Long noncoding RNA (lncRNA) PTTG3P has been demonstrated to participate in the development of hepatocellular carcinoma (HCC) by targeting the mRNA PTTG1. The present study aimed to investigate the diagnostic efficacy of serum lncRNA PTTG3P, mRNA PTTG1 and their combination for the diagnosis and prognosis of HCC. A total of 373 participants were enrolled in the present study, including 73 patients with HCC, 100 patients with chronic hepatitis B (CHB), 100 patients with liver cirrhosis (LC) and 100 healthy controls (HCs). The expression levels of serum RNAs were quantified by reverse transcription‑quantitative PCR. The association between serum lncRNA PTTG3P and clinical characteristics was further analyzed. Receiver operating characteristic (ROC) curve and area under curve (AUC) analyses were performed to estimate the diagnostic ability of serum lncRNA PTTG3P, PTTG1 and their combinations with other biomarkers for HCC. The results revealed that the expression levels of lncRNA PTTG3P and mRNA PTTG1 were markedly increased in the serum of patients with HCC and CHB compared with in the serum of HCs. Additionally, the postoperative levels of lncRNA PTTG3P and mRNA PTTG1 were significantly lower than the preoperative concentrations in 36 paired patients with HCC. Spearman's correlation coefficient analysis showed that serum lncRNA PTTG3P was correlated with aspartate transaminase (AST). ROC analysis showed that both lncRNA PTTG3P and mRNA PTTG1 had a significant predictive value for HCC. The AUC values of lncRNA PTTG3P and mRNA PTTG1 alone were 0.636 and 0.634, respectively. Furthermore, combining lncRNA PTTG3P, mRNA PTTG1, α‑fetoprotein (AFP), alanine aminotransferase (ALT), AST, γ‑glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) significantly increased the AUC value. The best performance was the combination of PTTG3P, PTTG1, AFP, ALT, AST, GGT and ALP with an AUC of 0.959, a sensitivity of 90.4% and a specificity of 98.0%. In conclusion, the combination of serum lncRNA PTTG3P, mRNA PTTG1 and AFP appeared to be a noninvasive biomarker with comparatively high specificity and sensitivity for the diagnosis of HCC.

More and more studies have demonstrated that pseudogenes possess coding ability, and the functions of their transcripts in the development of diseases have been partially revealed. However, the role of pseudogenes in maintenance of normal physiological states and life activities has long been neglected. Here, we identify pseudogenes that are dynamically expressed during human early embryogenesis, showing different expression patterns from that of adult tissues. We explore the expression correlation between pseudogenes and the parent genes, partly due to their shared gene regulatory elements or the potential regulation network between them. The essential role of three pseudogenes, PI4KAP1, TMED10P1, and FBXW4P1, in maintaining self-renewal of human embryonic stem cells is demonstrated. We further find that the three pseudogenes might perform their regulatory functions by binding to proteins or microRNAs. The pseudogene-related single-nucleotide polymorphisms are significantly associated with human congenital disease, further illustrating their importance during early embryonic development. Overall, this study is an excavation and exploration of functional pseudogenes during early human embryonic development, suggesting that pseudogenes are not only capable of being specifically activated in pathological states, but also play crucial roles in the maintenance of normal physiological states.

This study aimed to identify prognostic signatures to predict the prognosis of patients with stomach adenocarcinoma (STAD), which is necessary to improve poor prognosis and offer possible treatment strategies for STAD patients.

The overlapping genes between the key model genes that were screened by the weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) whose expression was different with significance between normal and tumor tissues were extracted to serve as co-expression genes. Then, enrichment analysis was performed on these genes. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression was performed to screen the hub genes among overlapping genes. Finally, we constructed a model to explore the influence of polygenic risk scores on the survival probability of patients with STAD, and interaction effect and mediating analyses were also performed.

DEGs included 2,899 upregulated genes and 2,896 downregulated genes. After crossing the DEGs and light-yellow module genes that were obtained by WGCNA, a total of 39 overlapping genes were extracted. The gene enrichment analysis revealed that these genes were enriched in the prion diseases, biosynthesis of unsaturated fatty acids, RNA metabolic process, hydrolase activity, etc. PIP5K1P1, PTTG3P, and SNORD15B were determined by LASSO-Cox. The prognostic prediction of the three-gene model was established. The Cox regression analysis showed that the comprehensive risk score for three genes was an independent prognosis factor.

PIP5K1P1, PTTG3P, and SNORD15B are related to the prognosis and overall survival of patients. The three-gene risk model constructed has independent prognosis predictive ability for STAD.

In the tumor microenvironment, the interplay among macrophages, cancer cells, and endothelial cells is multifaceted. Tumor-associated macrophages (TAMs), which often exhibit an M2 phenotype, contribute to tumor growth and angiogenesis, while cancer cells and endothelial cells reciprocally influence macrophage behavior. This complex interrelationship highlights the importance of targeting these interactions for the development of novel cancer therapies aimed at disrupting tumor progression and angiogenesis. Accumulating evidence underscores the indispensable involvement of lncRNAs in shaping macrophage functionality and contributing to the development of cancer. Animal studies have further validated the therapeutic potential of manipulating macrophage lncRNA activity to ameliorate disease severity and reduce morbidity rates. This review provides a survey of our current understanding of macrophage-associated lncRNAs, with a specific emphasis on their molecular targets and their regulatory impact on cancer progression. These lncRNAs predominantly govern macrophage polarization, favoring the dominance of M2 macrophages or TAMs. Exosomes or extracellular vesicles mediate lncRNA transfer between macrophages and cancer cells, affecting cellular functions of each other. Moreover, this review presents therapeutic strategies targeting cancer-associated lncRNAs. The insights and findings presented in this review pertaining to macrophage lncRNAs can offer valuable information for the development of treatments against cancer.

Non-small cell lung cancer (NSCLC) is a highly lethal disease worldwide. We found the pseudogene-derived lncRNA PTTG3P is upregulated in NSCLC and associated with larger tumor size, advanced staging, and poor prognosis. This study investigated the oncogenic roles and mechanisms of PTTG3P in NSCLC. We demonstrate that PTTG3P promoted NSCLC cell proliferation, migration, tumorigenesis, and metastasis while inhibiting apoptosis in vitro and in vivo. Mechanistically, PTTG3P formed an RNA-protein complex with ILF3 to maintain MAP2K6 and E2F1 mRNA stability, two oncogenic factors involved in NSCLC progression. RNA-seq revealed MAP2K6 and E2F1 were downregulated upon PTTG3P knockdown. RIP and RNA stability assays showed PTTG3P/ILF3 interaction stabilized MAP2K6 and E2F1 transcripts. Interestingly, E2F1 transcriptionally upregulated PTTG3P by binding its promoter, forming a positive feedback loop. Knockdown of E2F1 or PTTG3P attenuated their mutual regulatory effects on cell growth and migration. Thus, a PTTG3P/ILF3/E2F1 axis enhances oncogene expression to promote NSCLC pathogenesis. Our study reveals PTTG3P exerts oncogenic functions in NSCLC via mRNA stabilization and a feedback loop, highlighting its potential as a prognostic biomarker and therapeutic target.

Metastasis is a multi-step phenomenon during cancer development leading to the propagation of cancer cells to distant organ(s). According to estimations, metastasis results in over 90% of cancer-associated death around the globe. Long non-coding RNAs (LncRNAs) are a group of regulatory RNA molecules more than 200 base pairs in length. The main regulatory activity of these molecules is the modulation of gene expression. They have been reported to affect different stages of cancer development including proliferation, apoptosis, migration, invasion, and metastasis. An increasing number of medical data reports indicate the probable function of LncRNAs in the metastatic spread of different cancers. Phytochemical compounds, as the bioactive agents of plants, show several health benefits with a variety of biological activities. Several phytochemicals have been demonstrated to target LncRNAs to defeat cancer. This review article briefly describes the metastasis steps, summarizes data on some well-established LncRNAs with a role in metastasis, and identifies the phytochemicals with an ability to suppress cancer metastasis by targeting LncRNAs.

Breast cancer is a malignant type with morbidity ranking the first of women globally. As widely acknowledged, there exist close links between ncRNA-mRNA axis and breast cancer. In this study, we first overviewed expression and prognostic values of pituitary tumor transforming gene (PTTGs) in breast cancer. Next, two binding miRNAs (miR-186-5p and miR-655-3p) of PTTG1 in breast cancer were identified. Subsequently, several potential upstream ncRNAs of PTTG1-miR-186-5p/miR-655-3p axis in breast cancer were successively screened out, consisting of 11 lncRNAs, 17 circRNAs and 12 pseudogene-derived RNAs. Enrichment analysis for downstream target genes of PTTG1-miR-186-5p/miR-655-3p axis revealed that this axis is associated with TGF-beta signaling and MAPK signaling pathways. Further investigation demonstrated AURKA was one of the most key hub genes. Collectively, we established a potential PTTG1-related ncRNA-mRNA regulatory network in breast cancer.

Long noncoding RNAs (lncRNAs) play critical factors in tumor progression and are ectopically expressed in malignant tumors. Until now, lncRNA pituitary tumor-transforming 3, pseudogene (PTTG3P) biological function in colorectal cancer (CRC) further needs to be clarified. qRT-PCR was used to measure the PTTG3P level and CCK-8, glucose uptake, lactate assay, adenosine triphosphate (ATP) assay, extracellular acidification rate (ECAR) assay, and xenograft mice model were adopted to evaluate the glycolysis and proliferation, and macrophage polarization were determined in CRC cells. Xenograft experiments were utilized to analyze tumor growth. Ectopic expression of PTTG3P was involved in CRC and related to dismal prognosis. Through gain- and loss-of-function approaches, PTTG3P enhanced cell proliferation and glycolysis through YAP1. Further, LDHA knockdown or glycolysis inhibitor (2-deoxyglucose (2-DG), 3-BG) recovered from PTTG3P-induced proliferation. And PTTG3P overexpression could facilitate M2 polarization of macrophages. Silenced PTTG3P decreased the level of inflammatory cytokines TNF-α, IL-1β and IL-6, and low PTTG3P expression related with CD8+ T, NK, and TFH cell infiltration. Besides, hypoxia-inducible factor-1α (HIF1A) could increase PTTG3P expression by binding to the PTTG3P promoter region. Hypoxia-induced PTTG3P contributes to glycolysis and M2 phenotype of macrophage, which proposes a novel approach for clinical treatment.

The long non-coding RNA (lncRNA) OGFRP1 has been found to promote malignancy in prostate cancer (PC) and other cancer types. How this lncRNA functions in the regulation of PC chemoresistance, however, is poorly defined.

qRT-PCR was employed to measure OGFRP1, miR-149-5p, and IL-6 expression in PC tissues and cells. IC50 values for paclitaxel and docetaxel in PC cells were assessed via a CCK-8 assay approach. Putative miR-149-5p binding targets were identified and validated through bioinformatics assays and luciferase reporter assays, respectively. The impact of OGFRP1 on PC chemoresistance in vivo was validated using a xenograft model system.

Docetaxel-resistant PC (PC/DR) cells and tissues exhibited reduced OGFRP1 expression and increased miR-149-5p expression. Knocking down OGFRP1 augmented the sensitivity of these PC cells to docetaxel and paclitaxel in vitro and in vivo. Mechanistically, OGFRP1 was found to bind and sequester miR-149-5p within PC/DR cells, thereby indirectly regulating IL-6 expression. Consistent with this model, the overexpression of IL-6 reversed the OGFRP1 knockdown-mediated reductions in docetaxel and paclitaxel IC50 values for these PC cells.

OGFRP1 can sequester miR-149-5p, thereby indirectly promoting IL-6 upregulation and thereby promoting chemoresistance in PC cells. This OGFRP1/miR-149-5p/IL-6 axis may thus be a promising target for therapeutic efforts aimed at PC chemosensitization and treatment.

Colorectal cancer (CRC) is among the most frequent cancers and is associated with high mortality particularly when being diagnosed in advanced stages. Although several environmental and intrinsic risk factors have been identified, the underlying cause of CRC is not clear in the majority of cases. Several studies especially in the recent decade have pointed to the role of epigenetic factors in this kind of cancer. Long non-coding RNAs (lncRNAs) as important contributors in the epigenetic mechanisms are involved in the initiation, progression and metastasis of CRC. Tens of oncogenic lncRNAs and a lower number of tumor suppressor lncRNAs have been recently identified to be dysregulated in CRC cells and tissues. Notably, expressions of a number of these transcripts have been dysregulated in serum samples of CRC patients, providing a non-invasive route for detection of this kind of cancer. The involvement of lncRNAs in the regulation of autophagy has provided them the ability to modulate response of CRC cells to chemotherapeutic modalities. In the current manuscript, we review the studies which evaluated the role of lncRNAs in the pathogenesis and progression of CRC to appraise their application as diagnostic/ prognostic markers.