• Cancer
• Chemotherapy
• LncRNA
• Polyphenol
• Quercetin

• Quercetin/pharmacology
• Quercetin/therapeutic use
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• Humans
• Neoplasms/drug therapy
• Neoplasms/genetics
• Neoplasms/pathology
• Gene Expression Regulation, Neoplastic/drug effects
• Animals
• Apoptosis/drug effects

• Bladder cancer
• Drug resistance
• Nuclear factor erythrocyte 2-associated factor 2 (Nrf2)
• Oxidative stress
• Therapeutic strategy

• Urinary Bladder Neoplasms/drug therapy
• Urinary Bladder Neoplasms/metabolism
• Urinary Bladder Neoplasms/pathology
• NF-E2-Related Factor 2/metabolism
• Humans
• DNA Damage
• Signal Transduction/drug effects

• Autophagy
• Cancer
• Chemo-resistance
• Exosome
• MicroRNA

• MicroRNAs/genetics
• MicroRNAs/metabolism
• Humans
• Autophagy/genetics
• Autophagy/physiology
• Animals
• Signal Transduction/genetics
• Neoplasms/genetics
• Neoplasms/pathology
• Neoplasms/metabolism

• Breast cancer
• Hypoxia
• Metastasis
• lncRNA TCONS_I2_00001955

• Humans
• Female
• Breast Neoplasms/pathology
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• Clinical Relevance
• Gene Expression Regulation, Neoplastic
• Hypoxia/genetics
• Cell Line, Tumor

• No. 81502271 the National Natural Science Foundation of China
• No. A2020485 the Medical Scientific Research Foundation of Guangdong Province, China

• HIF-1
• angiogenesis
• bladder cancer
• drug resistance
• glucose metabolism
• metastasis
• proliferation
• treatment.

• Humans
• Urinary Bladder Neoplasms/metabolism
• Urinary Bladder Neoplasms/genetics
• Urinary Bladder Neoplasms/pathology
• Urinary Bladder Neoplasms/drug therapy
• Hypoxia-Inducible Factor 1/metabolism
• Gene Expression Regulation, Neoplastic
• Animals
• Neovascularization, Pathologic/metabolism
• Neovascularization, Pathologic/genetics
• Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
• Hypoxia-Inducible Factor 1, alpha Subunit/genetics

• YNWR-MY-2020-055 Special project of the "Ten Thousand Talents Plan" in Yunnan Province

• DNA damage and repair
• Hypoxia
• genomic instability
• non-coding RNAs
• phenotypes
• tumor hypoxia
• tumor microenvironment

• Humans
• RNA, Long Noncoding/genetics
• Gene Expression Regulation, Neoplastic
• Neoplasms/genetics
• Neoplasms/metabolism
• RNA, Untranslated/genetics
• Hypoxia/genetics
• DNA Damage/genetics
• Cell Hypoxia/genetics
• Genomic Instability
• Hypoxia-Inducible Factor 1, alpha Subunit/genetics
• Tumor Microenvironment/genetics

• Bladder cancer
• Competing endogenous RNA
• Therapeutic target
• lncRNA
• miRNA

Long non-coding RNAs (lncRNA) have recently been identified as key regulators of oxidative stress in several malignancies. The level of reactive oxygen species (ROS) must be constantly regulated to maintain cancer cell proliferation and chemoresistance and to prevent apoptosis. This review will discuss how lncRNAs alter the ROS level in cancer cells. We will first describe the role of lncRNAs in the nuclear factor like 2 (Nrf-2) coordinated antioxidant response of cancer cells. Secondly, we show how lncRNAs can promote the Warburg effect in cancer cells, thus shifting the cancer cell’s “building blocks” towards molecules important in oxidative stress regulation. Lastly, we explain the role that lncRNAs play in ROS-induced cancer cell apoptosis and proliferation.

• ROS
• antioxidant response
• cancer metabolism
• chemoresistance
• lncRNAs

• bladder urothelial carcinoma
• hypoxia
• lncRNA
• nomogram
• overall survival
• prognostic signature

• Hypoxia
• Hypoxia-inducible factors
• Immunotherapy
• Personalized medicine
• Tumor disease

During the process of tumor growth, cancer cells will be subjected to intermittent hypoxia. This results from the delay in the development of the vascular network in relation to the proliferation of cancer cells. The hypoxic nature of a tumor has been demonstrated as a negative factor for patient survival. To evaluate the impact of hypoxia on the survival and migration properties of low and high-grade bladder cancer cell lines, two low-grade (MGHU-3 and SW-780) and two high-grade (SW-1710 and T24) bladder cancer cell lines were cultured in normoxic (20% O₂) or hypoxic atmospheric conditions (2% O₂). The response of bladder cancer cell lines to hypoxic atmospheric cell culture conditions was examined under several parameters, including epithelial-mesenchymal transition, doubling time and metabolic activities, thrombospondin-1 expression, whole Matrix Metallo-Proteinase activity, migration and resistance to oxidative stress. The low-grade cell line response to hypoxia was heterogeneous even if it tended to adopt a more aggressive profile. Hypoxia enhanced migration and pro-survival properties of MGHU-3 cells, whereas these features were reduced for the SW-780 cell line cultured under low oxygen tension. The responses of tested high-grade cell lines were more homogeneous and tended to adopt a less aggressive profile. Hypoxia drastically changed some of the bladder cancer cell line properties, for example matrix metalloproteinases expression for all cancer cells but also switch in glycolytic metabolism of low grade cancer cells. Overall, studying bladder cancer cells in hypoxic environments are relevant for the translation from in vitro findings to in vivo context.

• NMIBC
• PPAR gamma
• classification
• clinical outcome
• copy number
• genomics
• non-muscle-invasive bladder cancer
• stage T1
• stage Ta
• transcriptomics

• Gene Dosage
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Muscles/pathology
• Mutation/genetics
• Mycobacterium bovis
• Neoplasm Invasiveness
• Neoplasm Proteins/genetics
• Neoplasm Recurrence, Local/pathology
• Neoplasm Staging
• PPAR gamma/genetics
• Transcription, Genetic
• Tumor Suppressor Protein p53/genetics
• Urinary Bladder Neoplasms/genetics
• Urinary Bladder Neoplasms/immunology
• Urinary Bladder Neoplasms/pathology
• Urinary Bladder Neoplasms/therapy

• 21777 Cancer Research UK

Colorectal cancer (CRC) is one of the most common diagnosed cancers around the world. The poor prognosis and high fatality caused by metastasis are still the challenges for clinical treatment. Therefore, it is promising to clarify the detailed molecular mechanism of CRC metastasis. Accumulating evidences indicate that long noncoding RNAs (lncRNAs) play important roles in cancer progression including CRC. In this study, the function of lncRNA UCA1 was investigated. UCA1 was confirmed to be highly expressed in colorectal cancer. Moreover, the UCA1 expression level was positively related to tumor stages. Silencing UCA1 showed inhibitory effect on cell proliferation and metastasis. Both UCA1 and NOTCH3 were validated as direct targets of miR-185. Silencing UCA1 repressed NOTCH3 expression through the miR-185 sponge. NOTCH3 was found to be highly expressed in CRC patients and positively related to UCA1 expression. Furthermore, HES5 was verified as a transcription factor of UCA1, which induced UCA1 expression. In conclusion, UCA1 is a direct target of HES5. UCA1 promotes CRC metastasis through regulating the miR-185/NOTCH3 axis.

With high rates of mortality and disability, stroke has caused huge social burden, and 85% of which is ischemic stroke. In recent years, it is a progressive discovery of long non-coding RNA (lncRNA) playing an important regulatory role throughout ischemic stroke. Hypoxia, generated from reduction or interruption of cerebral blood flow, leads to changes in lncRNA expression, which then influence disease progression. Therefore, we reviewed studies on expression of hypoxia-related lncRNAs and relevant molecular mechanism in ischemic stroke. Considering that hypoxia-inducible factor (HIF) is a crucial regulator in hypoxic progress, we mainly focus on the HIF-related lncRNA which regulates the expression of HIF or is regulated by HIF, further reveal their pathogenesis and adaption after brain ischemia and hypoxia, so as to find effective biomarker and therapeutic targets.

• HIF
• Hypoxia
• Ischemic stroke
• Long non coding RNA

• Long non-coding RNA
• Mycotoxins
• Oxidative stress
• Target
• Toxicity mechanism

Long non-coding RNAs (lncRNAs) belong to an extremely heterogeneous class of non-coding RNAs with a length ranging from 200 to 100,000 bp. They modulate a series of cellular pathways in both physiological and pathological context. It is no coincidence that they are expressed in an aberrant way in pathologies such as cancer, so as to deserve to be subclassified as oncogenes or tumor suppressors. These molecules are also involved in the regulation of cancer cell proliferation. Several lncRNAs are able to modulate cell growth both positively and negatively, and in this review we have focused on a small group of them, characterized by the simultaneous action on different pathways regulating cell proliferation. They have been considered in the light of their behavior in three different subtypes of proliferative pathways that we can define as (I) tumor suppressor, (II) oncogenic and (III) transcriptionally-driven. More specifically, we have characterized some lncRNAs considered oncogenes (such as H19, linc-ROR, MALAT1, HULC, HOTAIR and ANRIL), tumor suppressors (such as MEG3 and lincRNA-p21), and both oncogenes/tumor suppressors (UCA1 and TUG1) in a little more detail. As can be understood from the review, the interactions between lncRNAs and their molecular targets, only in the context of controlling cell proliferation, give rise to an intricate molecular network, the understanding of which, in the future, will certainly be of help for the treatment of molecular diseases such as cancer.

• Long non-coding RNA (lncRNA)
• cancer
• cell proliferation

• Keap1-Nrf2
• ROS
• bladder cancer
• oxidative stress
• sulforaphane

• biomarkers
• bladder cancer
• epigenetics
• metabolic pathways
• metabolism
• metabolomics
• miRNAs

• intra uterine growth restriction
• non-coding RNAs
• placenta
• preeclampsia
• syncytialisation
• trophoblast

The noncoding RNA termed urothelial carcinoma-associated 1 (UCA1) is an oncogenic lncRNA involved in promoting the growth of several tumors through various pathways. The aim of this study was to explore the expression of UCA1 in hypoxic breast cancer and its impact on tumorigenesis in low levels of oxygen. Here, we show that UCA1 is upregulated in a number of hypoxic (1% O₂) breast cancer cells. In addition, UCA1 expression is significantly overexpressed in breast cancer tissues compared to matched normal cells. UCA1 knockdown in hypoxia inhibits breast cancer proliferation and induces apoptosis. The knockdown of hypoxia-inducible transcription factor 1α (HIF-1α) but not HIF-2α significantly decreases the expression of UCA1 in hypoxia. Overall, these findings indicate that UCA1 is a hallmark of hypoxic breast cancer and its expression is positively regulated by HIF-1α.

• Cancer
• Circular RNA
• Long non-coding RNA
• MicroRNA
• SOX9
• Transcription factor

• Colorectal cancer
• HK2
• LDHA
• glycolysis
• lncRNA UCA1
• paclitaxel resistance

LncRNAs are defined as non-coding RNAs that are longer than 200 nucleotides in length. The previous studys has shown that lncRNAs played important roles in the regulation of gene expression and were essential in mammalian development and disease processes. Inspired by the observation that lncRNAs are aberrantly expressed in tumors, we extracted RNA from Bladder urothelial carcinoma and matched histologically normal urothelium from each patient and bladder carcinoma cell lines. Then, we reversed transcribed them into cDNA.Last, we investigated the expression patterns of ERIC by the fluorescence quantitative PCR in bladder cancer tissues and cell lines. CRISPR-dCas9-VPR targeting ERIC plasmid was transfected into T24 and 5637 cells, and cells were classified into two groups: negative control (NC) and ERIC overexpression group. MTT assay, transwell assay, and flow cytometry were performed to examine changes in cell proliferation, invasiveness, and apoptosis. We found that the expression of ERIC was down-regulated in bladder urothelial carcinoma compared to matched histologically normal urotheliam. The differences of the expression of this gene were large in the bladder cancer lines. Compared with the negative control group, the ERIC overexpression group showed significantly decreased cell proliferation rate (t = 7.583, p = 0.002; t = 3.283, p = 0.03) and invasiveness (t = 11.538, p < 0.001; t = 8.205, p = 0.01); and increased apoptotic rate (t = −34.083, p < 0.001; t = −14.316, p < 0.001). Our study lays a foundation for further study of its pathogenic mechanism in bladder cancer.

• CRISPR-dCas9-VPR
• ERIC
• bladder
• cancer
• long non coding RNA

Cancer is caused by the rapid and uncontrolled growth of cells that eventually lead to tumor formation. Genetic and epigenetic alterations are among the most critical factors in the onset of carcinoma. Phytochemicals are a group of natural compounds that play an essential role in cancer prevention and treatment. Long non-coding RNAs (lncRNAs) are potential therapeutic targets of bioactive phytochemicals, and these compounds could regulate the expression of lncRNAs directly and indirectly. Here, we critically evaluate in vitro and in vivo anticancer effects of phytochemicals in numerous human cancers via regulation of lncRNA expression and their downstream target genes.

Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs that play an essential role in various cellular activities, such as differentiation, proliferation, and apoptosis. Dysregulation of lncRNAs serves a fundamental role in the progression and initiation of various diseases, including cancer. Precision medicine is a suitable and optimal treatment method for cancer so that based on each patient’s genetic content, a specific treatment or drug is prescribed. The rapid advancement of science and technology in recent years has led to many successes in this particular treatment. Phytochemicals are a group of natural compounds extracted from fruits, vegetables, and plants. Through the downregulation of oncogenic lncRNAs or upregulation of tumor suppressor lncRNAs, these bioactive compounds can inhibit metastasis, proliferation, invasion, migration, and cancer cells. These natural products can be a novel and alternative strategy for cancer treatment and improve tumor cells’ sensitivity to standard adjuvant therapies. This review will discuss the antineoplastic effects of bioactive plant secondary metabolites (phytochemicals) via regulation of expression of lncRNAs in various human cancers and their potential for the treatment and prevention of human cancers.

• cancer treatment
• lncRNAs
• natural products
• phytochemicals
• precision medicine
• targeted therapy

Hypoxia, a characteristic of the tumour microenvironment, plays a crucial role in cancer progression and therapeutic response. The hypoxia-inducible factors (HIF-1α, HIF-2α, and HIF-3α), are the master regulators in response to low oxygen partial pressure, modulating hypoxic gene expression and signalling transduction pathways. HIFs’ activation is sufficient to change the cell phenotype at multiple levels, by modulating several biological activities from metabolism to the cell cycle and providing the cell with new characteristics that make it more aggressive. In the past few decades, growing numbers of studies have revealed the importance of non-coding RNAs (ncRNAs) as molecular mediators in the establishment of hypoxic response, playing important roles in regulating hypoxic gene expression at the transcriptional, post-transcriptional, translational, and posttranslational levels. Here, we review recent findings on the different roles of hypoxia-induced ncRNAs in cancer focusing on the data that revealed their involvement in tumour growth.

• HIF
• cancer
• cell cycle
• hypoxia
• lncRNAs
• miRNAs
• proliferation

• Basic Helix-Loop-Helix Transcription Factors/genetics
• Basic Helix-Loop-Helix Transcription Factors/metabolism
• Cell Hypoxia
• Cell Survival
• Humans
• Neoplasm Proteins/genetics
• Neoplasm Proteins/metabolism
• Neoplasms/genetics
• Neoplasms/metabolism
• Neoplasms/pathology
• RNA, Neoplasm/genetics
• RNA, Neoplasm/metabolism
• RNA, Untranslated/genetics
• RNA, Untranslated/metabolism
• Signal Transduction
• Tumor Microenvironment

• CRISPR
• genome editing
• malignancy
• mutations
• therapeutic tool
• therapy

• BNIP3
• HABON
• HIF-1α
• Hepatocarcinoma
• hypoxia
• lncRNA

• Cancer
• Long non-coding RNAs
• Non-coding RNAs
• Therapy
• microRNAs
• piRNAs
• snoRNAs

• Humans
• MicroRNAs/antagonists & inhibitors
• MicroRNAs/genetics
• Molecular Targeted Therapy
• Neoplasms/genetics
• Neoplasms/pathology
• Neoplasms/therapy
• RNA, Circular/antagonists & inhibitors
• RNA, Circular/genetics
• RNA, Long Noncoding/antagonists & inhibitors
• RNA, Long Noncoding/genetics
• RNA, Small Interfering/antagonists & inhibitors
• RNA, Small Interfering/genetics
• RNA, Untranslated/antagonists & inhibitors
• RNA, Untranslated/genetics

• R01 CA072851 NCI NIH HHS
• R01 CA181572 NCI NIH HHS
• R01 CA184792 NCI NIH HHS
• R01 CA202797 NCI NIH HHS

• Hypoxia
• hypoxia-inducible factor 1α
• microarray
• uroplakin 1A
• uroplakin 1A antisense RNA 1

• Cell Hypoxia/genetics
• Cell Line, Tumor
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
• Lung Neoplasms/genetics
• Methylation
• RNA Stability/genetics
• RNA, Antisense/genetics
• RNA, Antisense/metabolism
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• RNA, Small Interfering/metabolism
• Reproducibility of Results
• Ribonucleases/metabolism
• Up-Regulation/genetics
• Uroplakin Ia/genetics

• HIF-1α
• Hallmarks of cancer
• Hypoxia
• lncRNA

• Cancer therapy
• Long non-coding RNAs
• Tumor microenvironment
• Tumor stroma
• Tumor-stroma crosstalk

• HIF
• glycolysis
• hypoxia
• metabolism

• HIF
• cancer
• hypoxia
• hypoxia-inducible factor
• lncRNA
• long non-coding RNA

Over the past few years, long non-coding RNAs (lncRNAs) are recognized as key regulators of gene expression at chromatin, transcriptional and posttranscriptional level with pivotal roles in various biological and pathological processes, including cancer. Hypoxia, a common feature of the tumor microenvironment, profoundly affects gene expression and is tightly associated with cancer progression. Upon tumor hypoxia, the central regulator HIF (hypoxia-inducible factor) is upregulated and orchestrates transcription reprogramming, contributing to aggressive phenotypes in numerous cancers. Not surprisingly, lncRNAs are also transcriptional targets of HIF and serve as effectors of hypoxia response. Indeed, the number of hypoxia-associated lncRNAs (HALs) identified has risen sharply, illustrating the expanding roles of lncRNAs in hypoxia signaling cascade and responses. Moreover, through extra-cellular vesicles, lncRNAs could transmit hypoxia responses between cancer cells and the associated microenvironment. Notably, the aberrantly expressed cellular or exosomal HALs can serve as potential prognostic markers and therapeutic targets. In this review, we provide an update of the current knowledge about the expression, involvement and potential clinical impact of lncRNAs in tumor hypoxia, with special focus on their unique molecular regulation of HIF cascade and hypoxia-induced malignant progression.

• Extracellular vesicles
• HAL
• HIF-1α
• Hypoxia-associated lncRNAs
• Long non-coding RNA
• Tumor hypoxia
• lncRNA

• Cancer
• Long non-coding RNA
• Metabolism

• Animals
• Humans
• Lipid Metabolism/genetics
• Lipid Metabolism/physiology
• Neoplasms/genetics
• Neoplasms/metabolism
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism

• Invasion
• Migration
• NRF2
• Proliferation
• Prostate cancer
• TUG1

Hypoxia is a classic characteristic of the tumor microenvironment with a significant impact on cancer progression and therapeutic response. Hypoxia-inducible factor-1 alpha (HIF-1α), the most important transcriptional regulator in the response to hypoxia, has been demonstrated to significantly modulate hypoxic gene expression and signaling transduction networks. In past few decades, growing numbers of studies have revealed the importance of noncoding RNAs (ncRNAs) in hypoxic tumor regions. These hypoxia-responsive ncRNAs (HRNs) play pivotal roles in regulating hypoxic gene expression at the transcriptional, posttranscriptional, translational and posttranslational levels. In addition, as a significant gene expression regulator, ncRNAs exhibit promising roles in regulating HIF-1α expression at multiple levels. In this review, we briefly elucidate the reciprocal regulation between HIF-1α and ncRNAs, as well as their effect on cancer cell behaviors. We also try to summarize the complex feedback loop existing between these two components. Moreover, we evaluated the biomarker potential of HRNs for the diagnosis and prognosis of cancer, as well as the potential clinical utility of shared regulatory mechanisms between HIF-1α and ncRNAs in cancer treatment, providing novel insights into tumorigenicity, which may lead to innovative clinical applications.

• HIF-1α
• carcinogenesis
• clinical practice
• ncRNA

• chemotherapy
• drug resistance
• lncRNA
• ovarian cancer
• precision medicine

• apoptosis
• lncRNA UCA1
• miR-204
• pediatric acute myeloid leukemia
• proliferation

• ANRIL
• DILC
• Epilepsy
• MALAT1
• NKILA
• PACER
• Refractory
• THRIL
• UCA1

• Angiopoietin-Like Protein 4/genetics
• Animals
• Basic Helix-Loop-Helix Transcription Factors/metabolism
• Breast Neoplasms/blood supply
• Cell Hypoxia/genetics
• Cell Line, Tumor
• Endothelial Cells
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
• Mice
• Neoplasm Metastasis/genetics
• Neovascularization, Pathologic/genetics
• Neovascularization, Pathologic/pathology
• RNA Polymerase II/metabolism
• RNA, Long Noncoding/metabolism
• Tumor Microenvironment/genetics
• Up-Regulation
• Vascular Endothelial Growth Factor A/genetics
• Xenograft Model Antitumor Assays

• R00 CA168746 NCI NIH HHS
• R01 CA222393 NCI NIH HHS
• R01 AG066166 NIA NIH HHS
• R35 GM124693 NIGMS NIH HHS
• R00 NS078049 NINDS NIH HHS

• colorectal cancer
• invasion
• migration
• myocardin-related transcription factor-A
• urothelial cancer associated 1

• Cancer
• UCA1
• Urothelial carcinoma-associated 1
• lncRNA

• Animals
• CRISPR-Cas Systems
• Gene Editing/methods
• Gene Transfer Techniques/trends
• Genetic Therapy/trends
• Humans

• UCA1
• cancer
• drug resistance
• invasion
• metabolism
• micro RNA
• proliferation

Tumor malignancies involve cancer cell growth, issue invasion, metastasis and often drug resistance. A great deal of effort has been placed on searching for unique molecule(s) overexpressed in cancer cells that correlate(s) with tumor cell-specific behaviors. Hyaluronan (HA), one of the major ECM (extracellular matrix) components have been identified as a physiological ligand for surface CD44 isoforms which are frequently overexpressed in malignant tumor cells during cancer progression. The binding interaction between HA and CD44 isoforms often stimulates aberrant cellular signaling processes and appears to be responsible for the induction of multiple oncogenic events required for cancer-specific phenotypes and behaviors. In recent years, both microRNAs (miRNAs) (with ~20–25 nucleotides) and long non-coding RNAs (lncRNAs) (with ~200 nucleotides) have been found to be abnormally expressed in cancer cells and actively participate in numerous oncogenic signaling events needed for tumor cell-specific functions. In this review, I plan to place a special emphasis on HA/CD44-induced signaling pathways and the presence of several novel miRNAs (e.g., miR-10b/miR-302/miR-21) and lncRNAs (e.g., UCA1) together with their target functions (e.g., tumor cell migration, invasion, and chemoresistance) during cancer development and progression. I believe that important information can be obtained from these studies on HA/CD44-activated miRNAs and lncRNA that may be very valuable for the future development of innovative therapeutic drugs for the treatment of matrix HA/CD44-mediated cancers.

• CD44
• LncRNA UCA1
• chemoresistance
• hyaluronan (HA)
• invasion
• miRNAs
• tumor progression