Colorectal cancer (CRC) is a common type of malignancy in Western nations with high incidence related to different factors as genetic, foods and pollution. Long non-coding RNAs (LncRNAs) play a significant role in cellular processes, oncogensis and can be used as biomarkers for cancer progression. The rationale of this study was to quantify the expression levels of miRNA 497 and LncRNAs (XIST-TSIX) as a sensitive and accurate markers for CRC diagnosis and correlated with serum FOXK1, CA19.9 and CEA compared with normal subjects. This study was carried outon100 participants, they were divided into two equal groups: Group (1): Patients were diagnosed with CRC and Group (2): Normal subjects as control. Tumor size, type, TNM staging, differentiation, levels of FOXK1and, CEA, CA19.9 were evaluated in serum. The RNA was extracted from the tissue of CRC patients for quantification expression of miRNA 497 and LncRNAs (XIST and TSIX) using qRT-PCR. Data obtained showed that, the expression levels of tissue miRNA 497, XIST, TSIX in combination with serum FOXK1, CA19.9 and CEA are good confirmatory non-invasive markers for CRC diagnosis. Sensitivity and specificity tests showed higher AUC values of miRNA 497 + XIST + TSIX + FOXK1 significantly than those of CA19.9 + CAE. It was concluded that, a rigorous assessment of these parameters could facilitate the discovery of non-invasive biomarkers for the early detection and prognosis of CRC, ultimately enhancing the protocols for early treatment decision-making.

The PD1/PD-L1 axis plays an important immunosuppressive role during the T-cell-mediated immune response, which is essential for the physiological homeostasis of the immune system. The biology of the immunological microenvironment is extremely complex and crucial for the development of treatment strategies for immunotherapy. Characterization of the immunological, genomic or transcriptomic landscape of cancer patients could allow discrimination between responders and non-responders to anti-PD-1/PD-L1 therapy. Immune checkpoint inhibitor (ICI) therapy has shown remarkable efficacy in a variety of malignancies in landmark trials and has fundamentally changed cancer therapy. Current research focuses on strategies to maximize patient selection for therapy, clarify mechanisms of resistance, improve existing biomarkers, including PD-L1 expression and tumor mutational burden (TMB), and discover new biomarkers. In this review, we focus on the function of the PD-1/PD-L1 signaling pathway and discuss the immunological, genomic, epigenetic and transcriptomic landscape in cancer patients receiving anti-PD-1/PD-L1 therapy. Finally, we provide an overview of the clinical trials testing the efficacy of antibodies against PD-1/PD-L1.

Infertility is a reproductive health problem that attracts worldwide attention. Polycystic ovary syndrome (PCOS) is a major cause of female infertility and patients with obesity and PCOS are particularly common in clinical practice. Long non-coding RNA (lncRNAs) are a functional core in cells that regulate gene expression, transcription, and chromatin modification processes, and participate in epigenetics, cell cycle, and cell differentiation. LncRNAs are assumed to play a role in the occurrence and development of PCOS; however, their specific mechanism of action remains to be elucidated.

High-throughput sequencing technology has been used to sequence and analyze lncRNAs in exosomes from the follicular fluid of patients with obesity and PCOS and those who underwent assisted reproductive therapy owing to male factors. Specific expression profiles of patients with obesity and PCOS were obtained and functional information analysis combined with a literature review were performed to screen for differentially expressed lncRNAs, which were validated using real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR).

High-throughput sequencing analysis revealed that compared to normal patients with male infertility, patients with obesity and PCOS had a total of 20 lncRNAs with significant expression differences in follicular fluid exosomes. Among them, 17 lncRNAs were upregulated and three were downregulated. Functional analysis showed that differentially expressed genes were mainly enriched in "cell metabolism," "cell adhesion," and other aspects: related gene pathways mainly involved Huntington's disease, Parkinson's disease, spliceosomes, non-alcoholic fatty liver disease, and ribosomes. Verification of differentially expressed lncRNAs revealed that the expression of lncRNAs TPT1-AS1, PTOV1-AS1, PTPRG-AS1, and SNHG14 in follicular fluid exosomes was consistent with the sequencing results.

A preliminary differential expression profile of lncRNAs in exosomes of patients with obesity and PCOS was established by transcriptomic analysis of these individuals. Our bioinformatics analysis results may be applicable to further study of the impact mechanism involving obesity and PCOS. These differentially expressed lncRNAs maybe served as potential biomarkers for in-depth studies of the occurrence, development on Follicle quality and function for patients with PCOS in the future.

Breast cancer is the second primary cause of cancer death among women. Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is a central regulator for X chromosome inactivation, and its abnormal expression is a primary feature of breast cancer. So far, the mechanism of XIST in breast cancer has not been fully elucidated. We attempted to illustrate the mechanism of XIST in breast cancer. The expressions of XIST, microRNA-455-3p (miR-455-3p) in breast cancer were measured using quantitative real-time PCR. The expressions of homeobox C4 (HOXC4) were assessed with immunohistochemical and Western blot. Also, the functions of XIST in breast cancer were assessed by Cell Counting Kit-8 analysis, colony formation assay, flow cytometry, Western blot, Transwell, and cell scratch assays. Meanwhile, the mechanism of XIST in breast cancer was validated using database analysis and dual-luciferase reporter assay. Furthermore, the function of XIST in breast cancer in vivo was estimated by tumor xenograft model, immunohistochemical assay, and hematoxylin-eosin staining. XIST and HOXC4 expressions were increased, but miR-455-3p expressions were decreased in breast cancer tissues and cells. Knocking down XIST restrained breast cancer cell proliferation, invasion, migration, epithelial-mesenchymal transformation (EMT), and induced cell cycle arrest at G0/G1. Meanwhile, XIST interacted with miR-455-3p, while miR-455-3p interacted with HOXC4. XIST knockdown repressed breast cancer cell proliferation, invasion, and EMT, while miR-455-3p inhibitor or HOXC4 overexpression abolished those impacts. HOXC4 overexpression also blocked the impacts of miR-455-3p mimic on breast cancer cell malignant behavior. In vivo experimental data further indicated that XIST knockdown repressed breast cancer cell tumorigenic ability, and decreased HOXC4 and p-SMAD3 (TGF-β/SMAD-related protein) expressions.XIST/miR-455-3p/HOXC4 facilitated breast cancer development by activating the TGF-β/SMAD pathway.

Pulmonary arterial hypertension (PAH) is a sex-biased disease with female sex as a significant risk factor. Increased expression of the long noncoding RNA X-inactive-specific transcript (Xist), as induced by an intersectin-1s protein fragment with proliferative potential (EHITSN), may explain the sexual dimorphism of female pulmonary artery endothelial cells (ECs) and at least in part, the imbalance sex/ratio of PAH. Xist is essential for X-chromosome inactivation and dosage compensation of X-linked genes. Herein, increased Xist expression was detected in a subset of ECs and lung tissue samples of male patients with PAH. The role of different Xist expression levels in ECs of male patients with PAH (ECPAH) was studied in several lines of male ECPAH in conjunction with molecular, biochemical, morphologic, and functional approaches. Male ECPAH showed on average 10.3-fold increase in high Xist versus low Xist, a significant association between Xist levels and their proliferative potential, and a heterogeneous methylation of the Xist/XIST antisense RNA (Tsix) locus. Interestingly, Xist up-regulation in male ECPAH decreased the expression of Krueppel-like factor 2 (Klf2), via EHITSN interaction with enhancer of zeste polycomb repressive complex 2 subunit (EZH2), the catalytic subunit of the polycomb repressive complex 2. Moreover, the studies demonstrate that EHITSN-triggered p38/ETS domain-containing protein Elk1/AP-1 transcription factor subunit (c-Fos) signaling is a pathologic mechanism central to ECPAH proliferation and the dynamic crosstalk with cell cycle regulatory proteins cyclin A1/cyclin D2 and Xist-EZH2-Klf2 interaction participate directly and differentially in establishing the proliferative profile of male ECPAH.

So far, long noncoding RNAs (lncRNAs) signatures in acute myeloid leukemia (AML) are poorly understood. The present study aims to explore the prognostic significance of eleven cancer-related lncRNAs in bone marrow (BM) samples from adult Egyptian AML patients.

In this study, we analyzed eleven lncRNAs using the qRT-PCR assay in the bone marrow (BM) of 79 de novo AML adult patients before receiving any therapy.

Five lncRNAs out of 11 were aberrantly expressed, and two lncRNAs influenced significantly the patient's overall survival (OS). LncRNA-XIST was favorable when overexpressed (in univariate and multivariate analysis, P-value = .001). LncRNA-GAS5 adversely affected the OS (only in multivariate analysis P-value = .02). Two other lncRNAs (UCA1 and HIFAL) impacted complete remission induction (CR) significantly in univariate analysis (P-value = .046 for both). Furthermore, lncRNA-UCA1 affected CR significantly in multivariate COX regression analysis (P-value = .004). The 4 previously mentioned lncRNAs were among the 9 downregulated lncRNAs. Instead, the only 2 upregulated lncRNAs (SNHG15, MALAT1) did not significantly influence neither CR induction nor OS. LncRNA-PTCSC3, a fifth lncRNA, emerged as the only one that could predict relapse occurrence in an upfront original BM sample.

Two lncRNAs out of eleven (lncRNA-XIST and GAS5) impacted OS, and two other lncRNAs (UCA1 and HIFAL) affected CR in adult de novo AML patients. LncRNA-PTCSC3 predict relapse, however, further validation is still required.

The marker genes associated with white adipocytes and brown adipocytes have been previously identified; however, these markers have not been updated in several years, and the differentiation process of preadipocytes remains relatively fixed. Consequently, there has been a lack of exploration into alternative differentiation schemes. In this particular study, we present a transcriptional signature specific to brown adipocytes and white adipocytes. Notably, our findings reveal that ZNF497, ZIC1, ZFY, UTY, USP9Y, TXLNGY, TTTY14, TNNT3, TNNT2, TNNT1, TNNI1, TNNC1, TDRD15, SOX11, SLN, SFRP2, PRKY, PAX3KLHL40, PAX3, INKA2-AS1, SOX11, and TDRD15 exhibit high expression levels in brown adipocytes. XIST, HOXA10, PCAT19, HOXA7, PLSCR3, and AVPR1A exhibited high expression levels in white adipocytes, suggesting their potential as novel marker genes for the transition from white to brown adipocytes. Furthermore, our analysis revealed the coordinated activation of several pathways, including the PPAR signaling pathway, focal adhesion, retrograde endocannabinoid signaling, oxidative phosphorylation, PI3K-Akt signaling pathway, and thermogenesis pathways, in brown adipocytes. Moreover, in contrast to prevailing culture techniques, we conducted a comparative analysis of the differentiation protocols for white preadipocytes and brown preadipocytes, revealing that the differentiation outcome remained unaffected by the diverse culture schemes employed. However, the expression levels of certain marker genes in both adipocyte types were found to be altered. This investigation not only identified potential novel marker genes for adipocytes but also examined the impact of different differentiation methods on preadipocyte maturation. Consequently, these findings offer significant insights for further research on the differentiation processes of diverse adipocyte subtypes.

As immune checkpoint inhibitors (ICI) emerge as a paradigm-shifting treatment option for patients with advanced or metastatic cancer, there is a growing demand for biomarkers that can distinguish which patients are likely to benefit. In the case of triple-negative breast cancer (TNBC), characterized by a lack of therapeutic targets, pembrolizumab approval for high-risk early-stage disease occurred regardless of PD-L1 status, which keeps the condition in a biomarker limbus. In this review, we highlight the participation of long non-coding RNAs (lncRNAs) in the regulation of the PD-1/PD-L1 pathway, as well as in the definition of prognostic immune-related signatures in many types of tumors, aiming to shed light on molecules that deserve further investigation for a potential role as biomarkers. We also conducted a bioinformatic analysis to investigate lncRNAs already investigated in PD-1/PDL-1 pathways in other cancer types, considering the TNBC molecular context. In this sense, from the generated data, we evidence here two lncRNAs, UCA1 and HCP5, which have not yet been identified in the context of the tumoral immune response in breast cancer. These candidates can be further explored to verify their use as biomarkers for ICI response. In this article, we present an updated review regarding the use of lncRNA as biomarkers of response to ICI, highlighting the versatility of using these molecules.

Cell membrane-associated RNA (mem-RNA) has been demonstrated to be cell-specific and disease-related and are considered as potential biomarkers for disease diagnostics, drug delivery, and cell screening. However, there is still a lack of methods specifically designed to extract mem-RNA from cells, limiting the discovery and applications of mem-RNA. In this study, we propose the first all-in-one solution for high-purity mem-RNA isolation based on two types of magnetic nanoparticles, named MREMB (Membrane-associated RNA Extraction based on Magnetic Beads), which achieved ten times enrichment of cell membrane components and over 90% recovery rate of RNA extraction. To demonstrate MREMB's potential in clinical research, we extracted and sequenced mem-RNA of typical breast cancer MCF-7, MDA-MB-231, and SKBR-3 cell lines and non-neoplastic breast epithelial cell MCF-10A. Compared to total RNA, sequencing results revealed that membrane/secreted protein-encoding mRNAs and long noncoding RNAs (lncRNAs) were enriched in the mem-RNA, some of which were significantly overexpressed in the three cancer cell lines, including extracellular matrix-related genes COL5A1 and lncRNA TALAM1. The results indicated that MREMB could enrich membrane/secreted protein-coding RNA and amplify the expression differences of related RNAs between cancer and non-neoplastic cells, promising for cancer biomarker discovery.

Despite the recent advances in cancer therapy, triple-negative breast cancers (TNBCs) are the most relapsing cancer sub-type. It is partly due to their propensity to develop resistance against the available therapies. An intricate network of regulatory molecules in cellular mechanisms leads to the development of resistance in tumors. Non-coding RNAs (ncRNAs) have gained widespread attention as critical regulators of cancer hallmarks. Existing research suggests that aberrant expression of ncRNAs modulates the oncogenic or tumor suppressive signaling. This can mitigate the responsiveness of efficacious anti-tumor interventions. This review presents a systematic overview of biogenesis and down streaming molecular mechanism of the subgroups of ncRNAs. Furthermore, it explains ncRNA-based strategies and challenges to target the chemo-, radio-, and immunoresistance in TNBCs from a clinical standpoint.

Long non-coding RNAs (lncRNAs) have been shown to play a regulatory role in various processes of human diseases. However, lncRNA experiments are inefficient, time-consuming and highly subjective, so that the number of experimentally verified associations between lncRNA and diseases is limited. In the era of big data, numerous machine learning methods have been proposed to predict the potential association between lncRNA and diseases, but the characteristics of the associated data were seldom explored. In these methods, negative samples are randomly selected for model training and the model is prone to learn the potential positive association error, thus affecting the prediction accuracy. In this paper, we proposed a cyclic optimization model of predicting lncRNA-disease associations (COPTLDA in short). In COPTLDA, the two-step training strategy is adopted to search for the samples with the greater probability of being negative examples from unlabeled samples and the determined samples are treated as negative samples, which are combined together with known positive samples to train the model. The searching and training steps are repeated until the best model is obtained as the final prediction model. In order to evaluate the performance of the model, 30% of the known positive samples are used to calculate the model accuracy and 10% of positive samples are used to calculate the recall rate of the model. The sampling strategy used in this paper can improve the accuracy and the AUC value reaches 0.9348. The results of case studies showed that the model could predict the potential associations between lncRNA and malignant tumors such as colorectal cancer, gastric cancer, and breast cancer. The predicted top 20 associated lncRNAs included 10 colorectal cancer lncRNAs, 2 gastric cancer lncRNAs, and 8 breast cancer lncRNAs.

Inflammation and immune evasion are major key players in breast cancer (BC) progression. Recently, the FDA approved the use of anti-programmed death-ligand 1 antibody (anti-PD-L1) and phosphoinositide 3-kinase (PI3K) inhibitors against aggressive BC. Despite the paradigm shift in BC treatments, patients still suffer from resistance, recurrence and serious immune-related adverse events. These obstacles require unravelling of the hidden molecular contributors for such therapy failure hence yielding therapeutics that are at least as efficient yet safer. Inflammasome pathway is activated when the pattern recognition receptor senses danger signals (danger-associated molecular patterns) from damagedRdying cells or pathogen-associated molecular patterns found in microbes, leading to secretion of the active pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). It has been shown throughout numerous studies that inflammasome pathway enhanced invasion, metastasis, provoked BC progression and therapy resistance. Additionally, inflammasomes upregulated the proliferative index ki67 and enhanced PD-L1 expression leading to immunotherapy resistance. IL-1β contributed to significant decrease in oestrogen receptor levels and promoted BC chemo-resistance. High levels of IL-18 in sera of BC patients were associated with worst prognosis. Stimulation of purinergic receptors and modulation of adipokines in obese subjects activated inflammasomes that evoked radiotherapy resistance and BC progression. The micro RNA miR-223-3p attenuated the inflammasome over-expression leading to lowered tumour volume and lessened angiogenesis in BC. This review sheds the light on the molecular pathways of inflammasomes and their impacts in distinct BC subtypes. In addition, it highlights novel strategies in treatment and prevention of BC.

Breast cancer is the most frequently diagnosed malignancy and the leading cause of cancer-related death in women worldwide. Breast cancer development and progression are mainly associated with tumor-intrinsic alterations in diverse genes and signaling pathways and with tumor-extrinsic dysregulations linked to the tumor immune microenvironment. Significantly, abnormal expression of lncRNAs affects the tumor immune microenvironment characteristics and modulates the behavior of different cancer types, including breast cancer. In this review, we provide the current advances about the role of lncRNAs as tumor-intrinsic and tumor-extrinsic modulators of the antitumoral immune response and the immune microenvironment in breast cancer, as well as lncRNAs which are potential biomarkers of tumor immune microenvironment and clinicopathological characteristics in patients, suggesting that lncRNAs are potential targets for immunotherapy in breast cancer.

Background: Breast cancer (BRCA) represents the most frequent diagnosed malignancy in women worldwide. Despite treatment advances, BRCAs eventually develop resistance to targeted therapies, resulting in poor prognosis. The identification of new biomarkers, like immune-related long non-coding RNAs (lncRNAs), could contribute to the clinical management of BRCA patients. In this report, we evaluated the LINC00426 expression in PAM50 BRCA subtypes from two clinical independent cohorts (BRCA-TCGA and GEO-GSE96058 datasets). Methods and results: Using Cox regression models and Kaplan-Meier survival analyses, we identified that LINC00426 expression was a consistent overall survival (OS) predictor in luminal B (LB) BRCA patients. Subsequently, differential gene expression and gene set enrichment analyses identified that LINC00426 expression was associated with different immune-related and cancer-related pathways and processes in LB BRCA. Additionally, the LINC00426 expression was correlated with the infiltration level of diverse immune cell populations, alongside immune checkpoint and cytolytic activity-related gene expression. Conclusion: This evidence suggests that LINC00426 is a potential biomarker of immune phenotype and an OS predictor in PAM50 LB BRCA.

Triple-negative breast cancer (TNBC) is a metastatic and intractable cancer with limited treatment options. Refractory cancer cells often express the immune checkpoint molecules programmed death-ligand 1 (PD-L1) and PD-L2, which inhibit the anticancer effects of T cells. Differentiation-inducing factors, originally found in Dictyostelium discoideum, and their derivatives possess strong antiproliferative activity, at least in part by reducing cyclin D1 expression in various cancer cells, but their effects on PD-L1/PD-L2 have not been examined. In this study, we investigate the effects of six DIF compounds (DIFs) on the expression of PD-L1/PD-L2 and cyclin D1/D3 in MDA-MB-231 cells, a model TNBC cell line.

MDA-MB-231 cells were incubated for 5 or 15 h with or without DIFs, and the mRNA expression of cyclin D1, PD-L1, and PD-L2 were assessed by quantitative polymerase chain reaction (qPCR). Whereas, MDA-MD-231 cells were incubated for 12 or 24 h with or without DIFs, and the protein expression of cyclins D1 and D3, PD-L1, and PD-L2 were assessed by Western blotting.

As expected, some DIFs strongly reduced cyclin D1/D3 protein expression in MDA-MB-231 cells. Contrary to our expectation, DIFs had little effect on PD-L1 mRNA expression or increased it transiently. However, some DIFs partially reduced glycosylated PD-L1 and increased non-glycosylated PD-L1 in MDA-MB-231 cells. The level of PD-L2 was very low in these cells.

Since PD-L1 glycosylation plays an important role in preventing T cells from attacking cancer cells, such DIFs may promote T cell attack on cancer cells in vivo.

Cancer immunotherapy is a major breakthrough in the history of tumor therapy in the last decade. Immune checkpoint inhibitors blocking CTLA-4/B7 or PD-1/PD-L1 pathways have greatly prolonged the survival of patients with different cancers. Long non-coding RNAs (lncRNAs) are abnormally expressed in tumors and play an important role in tumor immunotherapy through immune regulation and immunotherapy resistance. In this review, we summarized the mechanisms of lncRNAs in regulating gene expression and well-studied immune checkpoint pathways. The crucial regulatory function of immune-related lncRNAs in cancer immunotherapy was also described. Further understanding of the underlying mechanisms of these lncRNAs is of great importance to the development of taking lncRNAs as novel biomarkers and therapeutic targets for immunotherapy.

In Iran, the delay in diagnosis and treatment of breast cancer results in low survival rates.

It is essential to characterize new therapeutic targets and prognostic breast cancer biomarkers. The rising evidence suggested that long non-coding RNAs (lncRNAs) expression levels are deregulated in human cancers and can use as biomarkers for the rapid diagnosis of breast cancer.

In the present study, a quantitative real-time polymerase chain reaction (qRT-PCR) technique was used to measure 20 oncogenic and tumor suppressor lncRNAs expression levels in whole blood samples of female breast cancer patients and healthy women. Receiver operating characteristic curve (ROC) was used to assess the diagnostic value of each selected lncRNA as a biomarker.

The results revealed that some circulating lncRNAs (MEG3, NBAT1, NKILA, GAS5, EPB41L4A-AS2, Z38, and BC040587) were significantly down-regulated in breast cancer patients compared to healthy women. In contrast, other circulating lncRNAs (H19, SPRY4-IT1, XIST, UCA1, AC026904.1, CCAT1, CCAT2, ITGB2-AS, and AK058003) were significantly up-regulated in breast cancer patients compared to controls. It was shown that the expression levels of NKILA, and NBAT1 lncRNAs were related to tumor size, and BC040587 expression level related to age, node metastasis, tumor size, and grade (p < .05). The association between H19 and SPRY4-IT1 lncRNAs with HER-2 was confirmed statistically (p < .05). ROC curves illustrated that the blood levels of SPRY4-IT1, XIST, and H19 lncRNAs have excellent potential in discriminating breast cancer from the healthy controls, showing an AUC of 1.0 (95% CI 1.0-1.0, p = .00), 0.898 (95% CI 0.815-0.981, p = .00), and 0.848 (95% CI 0.701-0.995, p = .01), respectively.

In conclusion, the expression levels of circulating H19 and SPRY4-IT1 lncRNAs in breast cancer patients could consider as the prognostic biomarkers and therapeutic targets in breast cancer, because of their excellent power in discriminating breast cancer from healthy individuals and the significant correlation of H19, and SPRY4-IT1 lncRNAs with clinicopathological traits. We also suggest the possible application of BC040587 lncRNA as a diagnostic and prognostic indicator to assess tumor progression in case of verification in larger patients' cohorts.

Accumulating evidence has demonstrated various associations of long non-coding RNAs (lncRNAs) with human diseases, such as abnormal expression due to microbial influences that cause disease. Gaining a deeper understanding of lncRNA-disease associations is essential for disease diagnosis, treatment, and prevention. In recent years, many matrix decomposition methods have also been used to predict potential lncRNA-disease associations. However, these methods do not consider the use of microbe-disease association information to enrich disease similarity, and also do not make more use of similarity information in the decomposition process. To address these issues, we here propose a correction-based similarity-constrained probability matrix decomposition method (SCCPMD) to predict lncRNA-disease associations. The microbe-disease associations are first used to enrich the disease semantic similarity matrix, and then the logistic function is used to correct the lncRNA and disease similarity matrix, and then these two corrected similarity matrices are added to the probability matrix decomposition as constraints to finally predict the potential lncRNA-disease associations. The experimental results show that SCCPMD outperforms the five advanced comparison algorithms. In addition, SCCPMD demonstrated excellent prediction performance in a case study for breast cancer, lung cancer, and renal cell carcinoma, with prediction accuracy reaching 80, 100, and 100%, respectively. Therefore, SCCPMD shows excellent predictive performance in identifying unknown lncRNA-disease associations.

Prometastatic and antitumor effects of different anesthetics have been previously analyzed in several studies with conflicting results. Thus, the underlying perioperative molecular mechanisms mediated by anesthetics potentially affecting tumor phenotype and metastasis remain unclear. It was hypothesized that anesthetic‑specific long non‑coding RNA (lncRNA) expression changes are induced in the blood circulation and play a crucial role in tumor outcome. In the present study, high‑throughput sequencing and quantitative PCR were performed in order to identify lncRNA and mRNA expression changes affected by two therapeutic regimes, total intravenous anesthesia (TIVA) and volatile anesthetic gas (VAG) in patients undergoing colorectal cancer (CRC) resection. Total blood RNA was isolated prior to and following resection and characterized using RNA sequencing. mRNA‑lncRNA interactions and their roles in cancer‑related signaling of differentially expressed lncRNAs were identified using bioinformatics analyses. The comparison of these two time points revealed 35 differentially expressed lncRNAs in the TIVA‑group, and 25 in the VAG‑group, whereas eight were shared by both groups. Two lncRNAs in the TIVA‑group, and 23 in the VAG‑group of in silico identified target‑mRNAs were confirmed as differentially regulated in the NGS dataset of the present study. Pathway analysis was performed and cancer relevant canonical pathways for TIVA were identified. Target‑mRNA analysis of VAG revealed a markedly worsened immunological response against cancer. In this proof‑of‑concept study, anesthesic‑specific expression changes in lncRNA and mRNA profiles in blood were successfully identified. Moreover, the data of the present study provide the first evidence that anesthesia‑induced lncRNA pattern changes may contribute further in the observed differences in CRC outcome following tumor resection.

Breast cancer is the frequent cause of disease burden related to cancer among women. It affects one in 20 women globally and up to one in eight women in high-income countries. Cuproptosis is a copper-induced modality of mitochondrial cell death that is involved in tumor proliferation and metastasis.

To construct a prognostic cuproptosis-related signature, LASSO Cox regression analysis was employed. Additionally, ceRNA was developed with an aim of exploring the possible lncRNA-miRNA-mRNA regulatory axis in breast cancer.

The expression of FDX1, DLD, DLAT, LIAS, LIPT1, GLS MTF1, and PDHA1 was downregulated, while CDKN2A expression level was elevated in breast cancer in contrast with normal tissue. We furthermore reviewed the genetic mutation landscape of genes linked to cuproptosis in breast cancer. Prognosis analysis revealed poor OS and RFS rates in breast cancer patients with elevated levels of CDKN2A and PDHA1 and low levels of MTF1, DLD, LIPT1, and FDX1. We then constructed a cuproptosis-related signature with six genes (DKN2A, MTF1, PDHA1, DLD, LIPT1, and FDX1) for breast cancer, which predicted the OS rate with an accuracy that ranged from medium to high. Further analysis demonstrated a significant correlation between the cuproptosis-related prognostic signature and pTNM stage, MSI score, drug sensitivity, TMB score, and immune cell infiltration. Moreover, we identified the lncRNA XIST/miR-92b-3p/MTF1 regulatory axis for breast cancer.

Multiomics approaches were used to create a cuproptosis-related signature with six genes (DKN2A, MTF1, PDHA1, DLD, LIPT1, and FDX1) for breast cancer. We discovered the lncRNA XIST/miR-92b-3p/MTF1 regulatory axis for breast cancer, which has not yet been investigated previously.

New research has indicated that long non-coding RNAs (lncRNAs) play critical roles in a broad range of biological processes, including the pathogenesis of many complex human diseases, including cancer. The detailed regulation mechanisms of many lncRNAs in cancer initiation and progression have yet to be discovered, even though a few of lncRNAs' functions in cancer have been characterized. In the present study, we summarize recent advances in the mechanisms and functions of lncRNAs in cancer. We focused on the roles of newly-identified lncRNAs as oncogenes and tumor suppressors, as well as the potential pathways these molecules could play. The paper also discusses their potential uses as biomarkers for the diagnosis and prognosis of cancer.

Long non-coding RNAs (lncRNAs) make up the majority of the human genome. They are a group of small RNA molecules that do not code for any proteins but play a primary role in regulating a variety of physiological and pathological processes. X-inactive specific transcript (XIST), one of the first lncRNAs to be discovered, is chiefly responsible for X chromosome inactivation: an evolutionary process of dosage compensation between the sex chromosomes of males and females. Recent studies show that XIST plays a pathophysiological role in the development and prognosis of brain tumors, a heterogeneous group of neoplasms that cause significant morbidity and mortality. In this review, we explore recent advancements in the role of XIST in migration, proliferation, angiogenesis, chemoresistance, and evasion of apoptosis in different types of brain tumors, with particular emphasis on gliomas.

Activation of brown adipose tissue (BAT) increases energy expenditure, which makes it an attractive therapeutic strategy for obesity. LncRNAs play an important role in adipocyte differentiation and regulation. Here we assessed the effect of lncRNA XIST on brown preadipocytes differentiation and metabolic regulation.

XIST expression levels were detected in human perirenal (peri-N) and subcutaneous adipose tissues (sub-Q), brown preadipocytes and 3T3-L1 preadipocytes. XIST overexpression and knockdown experiments were performed in brown preadipocytes. XIST overexpression mouse model was established by plasmid injection through tail vein.

In human adipose tissues, XIST expression was significantly higher in female than in male individuals. In vitro, XIST expression was significantly up-regulated during brown adipocyte differentiation. XIST knockdown inhibited differentiation of brown preadipocytes, while overexpression of XIST promotes brown preadipocytes to fully differentiation. RNA Binding Protein Immunoprecipitation (RIP) experiment revealed that XIST could directly bind to C/EBPα. In vivo, XIST overexpression prevents high-fat diet induced obesity and improves metabolic dysorder in male mice.

Our results suggest that XIST combats obesity through BAT activation at least partly by combination with transcription factor C/EBPα.

Long non-coding RNAs (LncRNAs) play a vital role in the process of malignant transformation. In breast cancer (BC), lncRNAs field is currently under intensive investigations. Yet, the role of lncRNAs as promising diagnostic and/or prognostic biomarkers and as therapeutic target/tool among BC patients still needs a special focus from the biomedical scientists. In BC, triple negative breast cancer patients (TNBC) are the unlucky group as they are always represented with the worst prognosis and the highest mortality rates. For that reason, a special focus on TNBC and associated lncRNAs was addressed in this review. Colon cancer-associated transcript 1 (CCAT-1) is a newly discovered oncogenic lncRNA that has been emerged as a vital biomarker for diagnosis, prognosis and therapeutic interventions in multiple malignancies and showed differential expression among TNBC patients. In this review, the authors shed the light onto the general role of lncRNAs in BC and the specific functional activities, molecular mechanisms, competing endogenous ncRNA role of CCAT-1 in TNBC.

Head and neck cancer (HNC) is one of the most prevalent cancers worldwide, accounting for approximately 5% of all cancers. While the underlying molecules and their pathogenetic mechanisms in HNC have yet to be well elucidated, recent studies have shown that dysregulation of lncRNAs may disrupt the homeostasis of various biological pathways. However, the understanding of lncRNAs in HNC is still limited by the lack of expression profiling. In the present study, we employed a systematic strategy to identify a panel of lncRNA associated with HNC. A cancer-related lncRNA profile PCR array was screened to explore potential molecules specific for HNC. A total of 55 lncRNAs were found to be dysregulated in HNC cells when compared to normal keratinocytes. Further analysis of the prognostic significance using The Cancer Genome Atlas (TCGA) database revealed 15 lncRNAs highly correlated with overall survival in HNC patients. Additionally, clinical sample expression analysis of the TCGA-HNSC cohort revealed 16 highly dysregulated lncRNAs in HNC, resulting in a combined 31-lncRNA signature panel that could predict prognosis. Validation of these molecules confirmed the considerable level of altered expressions in HNC cells, with XIST, HOXA11-AS, TSIX, MALAT1, WT1-AS, and IPW being the most prominently dysregulated. We further selected a molecule from our panel (XIST) to confirm the validity of these lncRNAs in the regulation of cancer aggressiveness. Gene ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses demonstrated that XIST participated in various cancer-related functions, including cell proliferation and metastasis. XIST silencing with the RNAi technique substantially reduced invasion and migration in several HNC cell lines. Thus, our study defined a 31-lncRNA panel as prognostic signatures in HNC. These perspective results provide a knowledge foundation for further application of these molecules in precision medicine.

Cancer immunotherapy has recently shown promising antitumor effects in various types of tumors. Among all immune checkpoints, the PD-1/PD-L1 pathway plays an important role in the immune evasion of tumor cells, making it a potent target in antitumor immunity. Accordingly, antibodies targeting the PD-1/PD-L1 pathway have been developed to attack tumor cells; however, resistance to immune therapy remains to be solved. Hence, identification of the underlying modulators of the PD-1/PD-L1 pathway is of significant importance to understand the mechanisms of antitumor immunotherapy. Long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have been identified to regulate the PD-1/PD-L1 pathway, leading to participation in the immune response and immunotherapy. Therefore, this review focuses on the functions of lncRNAs and circRNAs in regulation of the PD-1/PD-L1 axis in tumorigenesis and tumor progression. We hope this review will stimulate research to supply more precise and effective cancer immune checkpoint therapies for a large number of tumors.

Long non-coding RNAs (lncRNAs) have attracted widespread attention as potential biological and pathological regulators. lncRNAs are involved in several biological processes in cancer. Triple negative breast cancer (TNBC) is characterized by strong heterogeneity and aggressiveness. At present, the implication of microRNAs (miRs) and lncRNAs in immunotherapy has been poorly studied. Nevertheless, the blockade of immune checkpoints, particularly that of the programmed cell-death protein-1/programmed cell-death ligand-1 (PD-L1) axis, is considered as a principle approach in breast cancer (BC) therapy. The present study aimed to investigate the interaction between immune-modulatory upstream signaling pathways of the PD-L1 transcript that could enhance personalized targeted therapy. MDA-MB-231 cells were transfected with miR-182-5p mimics followed by RNA extraction and cDNA synthesis using a reverse transcription kit, and the expression levels of the target genes were assessed by reverse transcription-quantitative PCR. Furthermore, the expression levels of target genes were measured in tissues derived from 41 patients with BC, including patients with luminal BC and TNBC, as well as their adjacent lymph nodes. The results revealed that the expression levels of miR-182-5p, PD-L1 and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) were upregulated in MDA-MB-231 cells and BC tissues. However, X-inactive specific transcript (XIST) expression was downregulated in cancer tissues and TNBC cells. Following co-transfection of cells with small interfering RNAs specific for each target gene and miR-182-5p antagomirs, the effect of miR-182-5p was abolished in the presence of lncRNAs. Therefore, the results of the present study indicated that although miR-182-5p exhibited an oncogenic effect, XIST exerted a dominant effect on the regulation of the PD-L1 signaling pathway via the inhibition of the oncogenic function of MALAT1.

Oleuropein, the main secoiridoid glucoside found in Olea europaea L., has attracted scientific community as a potential anticancer agent. Immunotherapy and RNA interference revolutionized cancer treatment. Success of PD-L1/PD-1 antibodies encouraged the investigation of PD-1/PD-L1 regulation by non-coding RNAs. This study aimed to verify the cytotoxic effect of oleuropein on MDA-MB-231 cell line and to unravel novel ceRNA interaction between miR-194-5p and XIST in breast cancer and their immunomodulatory effect on PD-L1 expression to propose a promising prophylactic and preventive role of Oleuropin in diet. For the first time, miR-194/Lnc-RNA XIST/PD-L1 triad was investigated in breast cancer, where miR-194 and PD-L1 levels were significantly upregulated in 21 BC-biopsies, yet XIST was downregulated. Ectopic expression of miR-194 enhanced cell function and viability with concomitant increase in PD-L1 expression yet XIST expression decreased, in contrast to miR-194 antagomirs that yielded opposite results. XIST knock-out elevated miR194-5p and PD-L1 levels. miR-194-5p mimics and XIST siRNAs co-transfection induced PD-L1 expression, while miR-194-5p mimics and TSIX siRNAs co-transfection showed opposite effect. Oleuropein showed anti-carcinogenic impact by decreasing miR-194 and PD-L1 levels while increasing XIST level. In conclusion, our study highlighted novel ceRNA interaction controlling PD-L1 expression in BC. Oleuropein is a promising nutraceutical for cancer therapy. Therefore, oleuropin represents a new nutri-epigenetic in immune-oncology that controls miR-194/XIST/PD-L1 loop in triple negative breast cancer.

Head and neck squamous cell carcinoma is one of the most common and fatal cancers worldwide. Even a multimodal approach consisting of standard chemo- and radiotherapy along with surgical resection is only effective in approximately 50% of the cases. The rest of the patients develop a relapse of the disease and acquire resistance to treatment. Especially this group of individuals needs novel, personalized, targeted therapy. The first step to discovering such solutions is to investigate the tumor microenvironment, thus understanding the role and mechanism of the function of coding and non-coding sequences of the human genome. In recent years, RNA molecules gained great interest when the complex character of their impact on our biology allowed them to come out of the shadows of the "junk DNA" label. Furthermore, long non-coding RNAs (lncRNA), specifically the intergenic subgroup (lincRNA), are one of the most aberrantly expressed in several malignancies, which makes them particularly promising future diagnostic biomarkers and therapeutic targets. This review contains characteristics of known and validated lincRNAs in HNSCC, such as XIST, MALAT, HOTAIR, HOTTIP, lincRNA-p21, LINC02487, LINC02195, LINC00668, LINC00519, LINC00511, LINC00460, LINC00312, and LINC00052, with a description of their prognostic abilities. Even though much work remains to be done, lincRNAs are important factors in cancer biology that will become valuable biomarkers of tumor stage, outcome prognosis, and contribution to personalized medicine.

Long non-coding RNAs (lncRNAs) regulate gene expression in a variety of ways at epigenetic, chromatin remodeling, transcriptional, and translational levels. Accumulating evidence suggests that lncRNA X-inactive specific transcript (lncRNA Xist) serves as an important regulator of cell growth and development. Despites its original roles in X-chromosome dosage compensation, lncRNA Xist also participates in the development of tumor and other human diseases by functioning as a competing endogenous RNA (ceRNA). In this review, we comprehensively summarized recent progress in understanding the cellular functions of lncRNA Xist in mammalian cells and discussed current knowledge regarding the ceRNA network of lncRNA Xist in various diseases. Long non-coding RNAs (lncRNAs) are transcripts that are more than 200 nt in length and without an apparent protein-coding capacity (Furlan and Rougeulle, 2016; Maduro et al., 2016). These RNAs are believed to be transcribed by the approximately 98-99% non-coding regions of the human genome (Derrien et al., 2012; Fu, 2014; Montalbano et al., 2017; Slack and Chinnaiyan, 2019), as well as a large variety of genomic regions, such as exonic, tronic, and intergenic regions. Hence, lncRNAs are also divided into eight categories: Intergenic lncRNAs, Intronic lncRNAs, Enhancer lncRNAs, Promoter lncRNAs, Natural antisense/sense lncRNAs, Small nucleolar RNA-ended lncRNAs (sno-lncRNAs), Bidirectional lncRNAs, and non-poly(A) lncRNAs (Ma et al., 2013; Devaux et al., 2015; St Laurent et al., 2015; Chen, 2016; Quinn and Chang, 2016; Richard and Eichhorn, 2018; Connerty et al., 2020). A range of evidence has suggested that lncRNAs function as key regulators in crucial cellular functions, including proliferation, differentiation, apoptosis, migration, and invasion, by regulating the expression level of target genes via epigenomic, transcriptional, or post-transcriptional approaches (Cao et al., 2018). Moreover, lncRNAs detected in body fluids were also believed to serve as potential biomarkers for the diagnosis, prognosis, and monitoring of disease progression, and act as novel and potential drug targets for therapeutic exploitation in human disease (Jiang W. et al., 2018; Zhou et al., 2019a). Long non-coding RNA X-inactive specific transcript (lncRNA Xist) are a set of 15,000-20,000 nt sequences localized in the X chromosome inactivation center (XIC) of chromosome Xq13.2 (Brown et al., 1992; Debrand et al., 1998; Kay, 1998; Lee et al., 2013; da Rocha and Heard, 2017; Yang Z. et al., 2018; Brockdorff, 2019). Previous studies have indicated that lncRNA Xist regulate X chromosome inactivation (XCI), resulting in the inheritable silencing of one of the X-chromosomes during female cell development. Also, it serves a vital regulatory function in the whole spectrum of human disease (notably cancer) and can be used as a novel diagnostic and prognostic biomarker and as a potential therapeutic target for human disease in the clinic (Liu et al., 2018b; Deng et al., 2019; Dinescu et al., 2019; Mutzel and Schulz, 2020; Patrat et al., 2020; Wang et al., 2020a). In particular, lncRNA Xist have been demonstrated to be involved in the development of multiple types of tumors including brain tumor, Leukemia, lung cancer, breast cancer, and liver cancer, with the prominent examples outlined in Table 1. It was also believed that lncRNA Xist (Chaligne and Heard, 2014; Yang Z. et al., 2018) contributed to other diseases, such as pulmonary fibrosis, inflammation, neuropathic pain, cardiomyocyte hypertrophy, and osteoarthritis chondrocytes, and more specific details can be found in Table 2. This review summarizes the current knowledge on the regulatory mechanisms of lncRNA Xist on both chromosome dosage compensation and pathogenesis (especially cancer) processes, with a focus on the regulatory network of lncRNA Xist in human disease.

Uterine leiomyoma (UL), as the most prevalent type of women's health disorders, is a benign tumor that originates from the smooth muscle cell layer of the uterus. A great number of associated complications are observed including infertility, miscarriage, bleeding, pain, dysmenorrhea, menorrhagia, and dyspareunia. Although the etiology of UL is largely undefined, environmental and genetic factors are witnessed to engage in the UL development. As long non-coding RNAs (lncRNAs) are involved in various types of cellular functions, in recent years, a great deal of attention has been drawn to them and their possible roles in UL pathogenesis. Moreover, they have illustrated their potential to be promising candidates for UL treatment. In this review paper, firstly, an overview of UL pathogenesis is presented. Then, the regulation of lncRNAs in UL and their possible mechanisms in cancer development are reviewed. Eventually, therapeutic approaches targeting lncRNAs in various cancers and UL are explored.

Immune evasion hallmark has grabbed wide attention in cancer progression on the clinical level. Accordingly, innate and adaptive immune cells isolation and manipulation is essential in order to assess their activity and role in the tumor microenvironment (TME). This could open a gate toward a personalized therapy by a simple aspiration of blood sample from patients. Here, we describe the isolation of peripheral blood mononuclear cells (PBMCs) using Ficoll plus media in order to achieve the highest yield of immune cells that can be further processed and used in isolation of specific immune cells such as macrophages and cytotoxic T cells (CD8+ cells). Among the highly metastatic macrophages are the M2. This protocol describes the optimized techniques to isolate monocytes from whole blood, differentiate them into M2. This is followed by genetic and epigenetic (using synthetic nucleotides of noncoding RNAs) manipulation of these isolated immune cells in a tumor culture media, in addition to measurement of released cytokines using specific ELISA kit. In the last decade, new groups of noncoding RNAs have been emerged which are microRNAs and long noncoding RNAs. First, they were known as "junk DNA" with unknown regulatory functions. Despite the limited knowledge of these molecules, basic expression profiling is proving to be clinically relevant to cancer diagnosis, metastasis, and prognosis. Here, we describe methods used in molecular biology to assess the epigenetic expression of ncRNAs and their impact on other messenger RNA transcripts in M2 macrophages that could serve as future biomarkers in the context of tumor biology and metastasis or could open a gate in the treatment of cancer.

Anti-programmed death therapy has thrust immunotherapy into the spotlight. However, such therapy has a modest response in hepatocellular carcinoma (HCC). Epigenetic immunomodulation is a suggestive combinatorial therapy with immune checkpoint blockade. Non-coding ribonucleic acid (ncRNA) driven regulation is a major mechanism of epigenetic modulation. Given the wide range of ncRNAs that co-opt in programmed cell-death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) regulation, and based on the literature, we hypothesized that miR-155-5p, miR-194-5p and long non-coding RNAs (lncRNAs) X-inactive specific transcript (XIST) and MALAT-1 are involved in a regulatory upstream pathway for PD-1/PD-L1. Recently, nutraceutical therapeutics in cancers have received increasing attention. Thus, it is interesting to study the impact of oleuropein on the respective study key players.

To explore potential upstream regulatory ncRNAs for the immune checkpoint PD-1/PD-L1.

Bioinformatics tools including microrna.org and lnCeDB software were adopted to detect targeting of miR-155-5p, miR-194-5p and lncRNAs XIST and MALAT-1 to PD-L1 mRNA, respectively. In addition, Diana tool was used to predict targeting of both aforementioned miRNAs to lncRNAs XIST and MALAT-1. HCC and normal tissue samples were collected for scanning of PD-L1, XIST and MALAT-1 expression. To study the interaction among miR-155-5p, miR-194-5p, lncRNAs XIST and MALAT-1, as well as PD-L1 mRNA, a series of transfections of the Huh-7 cell line was carried out.

Bioinformatics software predicted that miR-155-5p and miR-194-5p can target PD-L1, MALAT-1 and XIST. MALAT-1 and XIST were predicted to target PD-L1 mRNA. PD-L1 and XIST were significantly upregulated in 23 HCC biopsies compared to healthy controls; however, MALAT-1 was barely detected. MiR-194 induced expression elevated the expression of PD-L1, XIST and MALAT-1. However, overexpression of miR-155-5p induced the upregulation of PD-L1 and XIST, while it had a negative impact on MALAT-1 expression. Knockdown of XIST did have an impact on PD-L1 expression; however, following knockdown of the negative regulator of X-inactive specific transcript (TSIX), PD-L1 expression was elevated, and abolished MALAT-1 activity. Upon co-transfection of miR-194-5p with siMALAT-1, PD-L1 expression was elevated. Co-transfection of miR-194-5p with siXIST did not have an impact on PD-L1 expression. Upon co-transfection of miR-194 with siTSIX, PD-L1 expression was upregulated. Interestingly, the same PD-L1 expression pattern was observed following miR-155-5p co-transfections. Oleuropein treatment of Huh-7 cells reduced the expression profile of PD-L1, XIST, and miR-155-5p, upregulated the expression of miR-194-5p and had no significant impact on the MALAT-1 expression profile.

This study reported a novel finding revealing that opposing acting miRNAs in HCC, have the same impact on PD-1/PD-L1 immune checkpoint by sharing a common signaling pathway.

Breast cancer (BC) remains a major health problem, despite the remarkable advances in cancer research setting. BC is the most common cancer affecting women worldwide. In the context of triple negative breast cancer (TNBC) treatment, major obstacles include late diagnoses and detrimental side effects of chemotherapy and radiotherapy. Research effort was rewarded with the discovery of mesothelin (MSLN), an oncogenic Glycosyl-Phosphatidyl-Inositol (GPI) anchored protein, over-expressed in TNBC. GPI pathway is a post-translational modification that attaches proteins to cellular membrane. MSLN targeted therapy succeeded in early clinical trials, nevertheless, to date, the epigenetic regulation of MSLN and GPI pathway by non-coding RNAs (nc-RNAs) in BC remains an untouched area. Accordingly, our aim is to investigate-for the first time- the impact of simultaneous targeting of MSLN and its associated GPI pathway member, PIG-C, by non-coding-RNAs. Expression profiling of PIG-C, MSLN in BC was performed. Using bioinformatics tools, MALAT-1 and miR-182 were found to target MSLN and PIG-C. MDA-MB-231 cells were transfected with synthetic nc-RNAs. Expression profiling of MSLN, miR-182 and MALAT-1 showed a dramatic over-expression in BC samples. MiR-182 ectopic expression and MALAT-1 silencing increased MSLN and PIG-C transcript levels. However, miR-182 inhibition and miR-182/si-MALAT-1 co-transfection lowered MSLN and PIG-C levels. Finally, si-PIG-C decreased MSLN and PIG-C levels. To conclude, our investigation unravels a new axis in TNBC, where miR-182 can manipulate MSLN and PIG-C. Meanwhile, MALAT-1 is the culprit lncRNA in this novel axis, possibly a sponge for miR-182. Altogether, this sheds light on new targets for BC immune-therapy.

Cancer stem cells (CSCs) are a small subpopulation of tumor cells critical for tumor development. Their unique abilities, such as self-renewal, have resulted in tumor resistance to various cancer treatments, including traditional chemotherapy and latest immunotherapy. CSCs-targeting therapy is a promising treatment to overcome the therapeutic resistances to different tumors. However, despite their significance, the regulatory mechanism generating therapy-resistant CSCs is still obscure. Long non-coding RNAs (lncRNAs) are key regulators in various biological processes, including cell proliferation, apoptosis, migration, and invasion. Recent studies have revealed that lncRNAs play an important role in the therapeutic resistance of CSCs. Here we summarize the latest studies on the regulatory role of lncRNAs in sustaining the stemness of CSCs, and discuss the associated mechanisms behind these behavior changes in CSCs-related chemo- and immune-resistance. Future research implications are also discussed, shedding light on the potential CSCs-targeted strategies to break through the resistance of current therapies.

Breast cancer (BC) is the most common female malignancy and the second leading cause of cancer-related death worldwide. In spite of significant advances in clinical management, the mortality of BC continues to increase due to the frequent occurrence of treatment resistance. Intensive studies have been conducted to elucidate the molecular mechanisms underlying BC therapeutic resistance, including increased drug efflux, altered drug targets, activated bypass signaling pathways, maintenance of cancer stemness, and deregulated immune response. Emerging evidence suggests that long noncoding RNAs (lncRNAs) are intimately involved in BC therapy resistance through multiple modes of action. Therefore, an in-depth understanding of the implication of lncRNAs in resistance to clinical therapies may improve the clinical outcome of BC patients. Here, we highlight the role and underlying mechanisms of lncRNAs in regulating BC treatment resistance with an emphasis on lncRNAs-mediated resistance in different clinical scenarios, and discuss the potential of lncRNAs as novel biomarkers or therapeutic targets to improve BC therapy response.

Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor that occurs in the head and neck. People living in areas with serious air pollution and those who smoke and drink for a long time belong to high-risk groups. Although great progress has been made in chemotherapy, radiotherapy, and molecular targeted therapy in recent years, the prognosis of patients is still not good. The proliferation, invasion, and apoptosis of LSCC are controlled by many factors, which are the key factors influencing the prognosis of patients. Previous researches have demonstrated that long noncoding RNAs (lncRNAs) can be used as oncogenes or tumor suppressor genes in the occurrence and development of cancer and regulate cancer through various ways including epigenetic regulation and post-transcriptional regulation. The characteristics and roles of lncRNAs in LSCC, however, are not clear. In this review, we will discuss the role and function of lncRNAs in the proliferation, invasion, and apoptosis of LSCC and analyze the relationship between lncRNAs and lncRNA-regulated signaling pathways in LSCC pathological process. The difficulties faced by the related research of LSCC are discussed. It provides reference ideas for the molecular mechanism research of LSCC targeting lncRNA and its signaling pathways, the development of clinical prevention and therapeutic drug and individualized treatment, thereby improving the quality of life of patients.