Zhenglong Li

LncRNA‐ATB: An indispensable cancer‐related long noncoding RNA

Long non‐coding RNAs (lncRNAs) are a group of non‐protein‐coding RNAs that are greater than 200 nucleotides in length. Increasing evidence indicates that lncRNAs, which may serve as either oncogenes or tumour suppressor genes, play a vital role in the pathophysiology of human diseases, especially in tumourigenesis and progression. Deregulation of lncRNAs impacts different cellular processes, such as proliferation, dedifferentiation, migration, invasion and anti‐apoptosis. The aim of this review was to explore the molecular mechanism and clinical significance of long non‐coding RNA‐activated by transforming growth factor β (lncRNA‐ATB) in various types of cancers.

SP1-induced upregulation of lncRNA SPRY4-IT1 exerts oncogenic properties by scaffolding EZH2/LSD1/DNMT1 and sponging miR-101-3p in cholangiocarcinoma

BackgroundAccumulating evidence has indicated that long non-coding RNAs (lncRNAs) behave as a novel class of transcription products during multiple cancer processes. However, the mechanisms responsible for their alteration in cholangiocarcinoma (CCA) are not fully understood.MethodsThe expression of SPRY4-IT1 in CCA tissues and cell lines was determined by RT-qPCR, and the association between SPRY4-IT1 transcription and clinicopathologic features was analyzed. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were performed to explore whether SP1 could bind to the promoter region of SPRY4-IT1 and activate its transcription. The biological function of SPRY4-IT1 in CCA cells was evaluated both in vitro and in vivo. ChIP, RNA binding protein immunoprecipitation (RIP) and luciferase reporter assays were performed to determine the molecular mechanism of SPRY4-IT1 in cell proliferation, apoptosis and invasion.ResultsSPRY4-IT1 was abnormally upregulated in CCA tissues and cells, and this upregulation was correlated with tumor stage and tumor node metastasis (TNM) stage in CCA patients. SPRY4-IT1 overexpression was also an unfavorable prognostic factor for patients with CCA. Additionally, SP1 could bind directly to the SPRY4-IT1 promoter region and activate its transcription. Furthermore, SPRY4-IT1 silencing caused tumor suppressive effects via reducing cell proliferation, migration and invasion; inducing cell apoptosis and reversing the epithelial-to-mesenchymal transition (EMT) process in CCA cells. Mechanistically, enhancer of zeste homolog 2 (EZH2) along with the lysine specific demethylase 1 (LSD1) or DNA methyltransferase 1 (DNMT1) were recruited by SPRY4-IT1, which functioned as a scaffold. Importantly, SPRY4-IT1 positively regulated the expression of EZH2 through sponging miR-101-3p.ConclusionsOur data illustrate how SPRY4-IT1 plays an oncogenic role in CCA and may offer a potential therapeutic target for treating CCA.

Long non-coding RNA UCA1 indicates an unfavorable prognosis and promotes tumorigenesis via regulating AKT/GSK-3β signaling pathway in cholangiocarcinoma

Long non-coding RNAs (lncRNAs) have been documented to play key roles in a wide range of pathophysiological processes, including cancer initiation and progression. Recently, the aberrant expression of urothelial carcinoma associated 1 (UCA1) was observed in many types of cancers. However, its clinical relevance and exact effects in cholangiocarcinoma (CCA) remains unknown. In the present study, we aimed to investigate the clinical significance of UCA1 and evaluate its prognostic value in patients with CCA. Besides, the functional roles of UCA1 were detected both in vitro and in vivo. Moreover, potential signaling pathways were explored to clarify the molecular mechanisms underlying CCA cell proliferation. The results indicated that UCA1 transcription is enhanced in both CCA tissue samples and cell lines, and this overexpression is associated with tumor stage (P = 0.007), lymph node invasion (P = 0.027), TNM stage (P = 0.004) and postoperative recurrence (P = 0.033) of CCA patients. Besides, UCA1 could function as an independent prognostic predictor for overall survival in patients with CCA (P = 0.014). For the part of functional assays, knockdown of UCA1 could attenuate CCA cell growth both in vitro and in vivo. Besides, UCA1 facilitates apoptosis via Bcl-2/caspase-3 pathway. In addition, UCA1 regulates migration and invasion potential of CCA cells by affecting EMT. Furthermore, AKT/GSK-3β axis was activated to upregulate CCND1 expression due to overexpression of UCA1 in CCA. To summary, UCA1 might be a potentially useful prognostic biomarker and therapeutic target for CCA.

The prognostic potential and carcinogenesis of long non-coding RNA TUG1 in human cholangiocarcinoma

Cholangiocarcinoma (CCA) is a fatal disease with increasing worldwide incidence and is characterized by poor prognosis due to its poor response to conventional chemotherapy or radiotherapy. Long non-coding RNAs (lncRNAs) play key roles in multiple human cancers, including CCA. Cancer progression related lncRNA taurine-up-regulated gene 1 (TUG1) was reported to be involved in human carcinomas. However, the impact of TUG1 in CCA is unclear. The aim of this study was to explore the expression pattern of TUG1 and evaluate its clinical significance as well as prognostic potential in CCA. In addition, the functional roles of TUG1 including cell proliferation, apoptosis, migration, invasion and epithelial-mesenchymal transition (EMT), were evaluated after TUG1 silencing. Our data demonstrated up-regulation of TUG1 in both CCA tissues and cell lines. Moreover, overexpression of TUG1 is linked to tumor size (p=0.005), TNM stage (p=0.013), postoperative recurrence (p=0.036) and overall survival (p=0.010) of CCA patients. Furthermore, down-regulation of TUG1 following RNA silencing reduced cell growth and increased apoptosis in CCA cells. Additionally, TUG1 suppression inhibited metastasis potential in vitro by reversing EMT. Overall, our results suggest that TUG1 may be a rational CCA-related prognostic factor and therapeutic target.Cholangiocarcinoma (CCA) is a fatal disease with increasing worldwide incidence and is characterized by poor prognosis due to its poor response to conventional chemotherapy or radiotherapy. Long non-coding RNAs (lncRNAs) play key roles in multiple human cancers, including CCA. Cancer progression related lncRNA taurine-up-regulated gene 1 (TUG1) was reported to be involved in human carcinomas. However, the impact of TUG1 in CCA is unclear. The aim of this study was to explore the expression pattern of TUG1 and evaluate its clinical significance as well as prognostic potential in CCA. In addition, the functional roles of TUG1 including cell proliferation, apoptosis, migration, invasion and epithelial-mesenchymal transition (EMT), were evaluated after TUG1 silencing. Our data demonstrated up-regulation of TUG1 in both CCA tissues and cell lines. Moreover, overexpression of TUG1 is linked to tumor size (p=0.005), TNM stage (p=0.013), postoperative recurrence (p=0.036) and overall survival (p=0.010) of CCA patients. Furthermore, down-regulation of TUG1 following RNA silencing reduced cell growth and increased apoptosis in CCA cells. Additionally, TUG1 suppression inhibited metastasis potential in vitro by reversing EMT. Overall, our results suggest that TUG1 may be a rational CCA-related prognostic factor and therapeutic target.

Long noncoding RNA PCAT1 regulates extrahepatic cholangiocarcinoma progression via the Wnt/β-catenin-signaling pathway

Extrahepatic cholangiocarcinoma (ECC) is a deadly disease that often responds poorly to conventional chemotherapy or radiotherapy. Long noncoding RNAs (lncRNAs) play important roles in human cancers, including ECC, and recent studies indicated that the lncRNA prostate cancer-associated transcript 1 (non-protein coding) (PCAT1) is involved in multiple cancers. However, the role of PCAT1 in ECC is unclear. Previously, we showed that PCAT1 is up-regulated in both ECC tissue samples and cell lines. Here, we showed that downregulation of PCAT1 following transfection with silencing RNA reduced ECC cell growth and increased cell apoptosis. Additionally, PCAT1 suppression inhibited ECC cell migration and invasion as determined by transwell assay. Furthermore, we determined that PCAT1 is a competing endogenous for microRNA (miR)-122, with bioinformatics analysis and luciferase-reporter assay results demonstrating that PCAT1 regulated WNT1 expression via miR-122. Moreover, PCAT1 downregulation increased levels of glycogen synthase kinase 3β and significantly decreased β-catenin levels in whole cell lysates and nuclear fractions, indicating that PCAT1 silencing inhibited the Wnt/β-catenin-signaling pathway. We also observed that exogenous expression of WNT1 reversed PCAT1-silencing-induced inhibition of ECC cell growth inhibition. These results indicated that PCAT1 silencing inhibited ECC progression by reducing Wnt/β-catenin signaling through miR-122 repression and WNT1 expression. Our findings revealed an important role of PCAT1 in ECC and suggested that PCAT1 might be a potential ECC-related therapeutic target.

ZEB1-AS1: A crucial cancer-related long non-coding RNA

Long non‐coding RNAs (lncRNAs) recently emerge as a novel class of non‐coding RNAs (ncRNAs) with larger than 200 nucleotides in length. Due to lack an obvious open reading frame, lncRNAs have no or limited protein‐coding potential. To date, accumulating evidence indicates the vital regulatory function of lncRNAs in pathological processes of human diseases, especially in carcinogenesis and development. Deregulation of lncRNAs not only alters cellular biological behavior, such as proliferation, migration and invasion, but also represents the poor clinical outcomes. Zinc finger E‐box binding homeobox 1 antisense 1 (ZEB1‐AS1), an outstanding cancer‐related lncRNA, is identified as an oncogenic regulator in diverse malignancies. Dysregulation of ZEB1‐AS1 has been demonstrated to exhibit a pivotal role in tumorigenesis and progression, suggesting its potential clinical value as a promising biomarker or therapeutic target for cancers. In this review, we make a summary on the current findings regarding the biological functions, underlying mechanisms and clinical significance of ZEB1‐AS1 in cancer progression.

Long non-coding RNA HOTAIR promotes tumorigenesis and forecasts a poor prognosis in cholangiocarcinoma

Cholangiocarcinoma (CCA) arising from the neoplastic transformation of cholangiocytes with increasing incidence in the worldwide. Unfortunately, a large amount of CCA patients lost their chance for surgery because it is hard to diagnose in the early stages. Long non-coding RNAs (lncRNAs) is closely associated with development and progression of various malignant tumors. Hox transcript antisense intergenic (HOTAIR), a negative prognostic factor for patients with gastric, liver and pancreatic carcinoma. Its transcription levels and functional roles in CCA is still unknown. Therefore, we aimed to explore the effect of HOTAIR in CCA including cell proliferation, apoptosis, migration, invasion and epithelial-to-mesenchymal transition (EMT). The results showed that HOTAIR was highly expressed both in CCA tissue samples and cell lines compared with corresponding normal bile duct tissues and Human intrahepatic biliary epithelial cells (HIBEC). Its overexpression was closely correlated with Tumor size, TNM stage and postoperative recurrence in CCA patients. Moreover, up-regulation of HOTAIR has correlation with prognosis in CCA patients. Knockdown of HOTAIR by siRNAs significantly decreased the migration and invasion but increased apoptosis of CCA cells in vitro. Overall, our study revealed that HOTAIR may play as a new potential therapeutic target and forecast poor prognosis for this fatal disease.

The role of long non-coding RNA AFAP1-AS1 in human malignant tumors

OBJECTIVES Long non-coding RNAs (lncRNAs) are a type Table of endogenous RNA longer than 200 nucleotides in length, and this kind of RNAs lack or possess limited ability of coding proteins. A large number of studies have demonstrated that lncRNAs could take part in massive biological processes, such as transcriptional activation and interference, cellular differentiation, proliferation, migration, invasion and apoptosis. The abnormal expression of lncRNAs has been clarified to play extremely important roles in various diseases, especially in human cancers. LncRNA actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) is a newly recognized cancer-related lncRNA deriving from the antisense strand of DNA at the AFAP1 coding gene locus. A slew of new studies suggest that AFAP1-AS1 is involved in many kinds of malignant tumors. Moreover, in recent years, the dysregulated expression of AFAP1-AS1 has been confirmed to be associated with oncogenesis and tumor progression. Evidence has increasingly shown that AFAP1-AS1 could probably serve as a novel potential molecular biomarker in tumor diagnosis and therapeutic target in tumor treatment. In this review, we sum up present stage new hottest research issues in respect of the biological functions and molecular mechanisms of AFAP1-AS1 in occurrence and progression of human tumors. MATERIALS AND METHODS In this review, we summarize the recent researches about the expression and molecular biological mechanisms of lncRNA AFAP1-AS1 in tumor development. Existing relevant studies are acquired and analyzed by searching Pubmed, BioMedNet, GEO database and Academic Search Elit systematically. RESULTS Long non-coding RNA AFAP1-AS1 is an important tumor-associated lncRNA and its aberrant expression has been found in many malignancies so far, including pancreatic ductal adenocarcinoma, cholangiocarcinoma, gallbladder cancer, hepatocellular carcinoma, gastric cancer, colorectal cancer, esophageal cancer, nasopharyngeal carcinoma, lung cancer, ovarian cancer, breast cancer, retinoblastoma, laryngeal cancer, tongue squamous cell carcinoma and thyroid cancer. In addition, the dysregulated expression of AFAP1-AS1 is related to carcinogensis, overall survival (OS), disease-free survival (DFS), progression-free survival (PFS) and tumor progression containing lymph node metastasis, distant metastasis, histological grade, tumor size and tumor stage. CONCLUSIONS A series of studies provide detailed information to understand lncRNA AFAP1-AS1 role in various human cancers. LncRNA AFAP1-AS1 is an oncogene in tumors that have been studied so far, and it may act as a useful tumor biomarker and therapeutic target.

Current insight into a cancer-implicated long noncoding RNA ZFAS1 and correlative functional mechanisms involved

OBJECTIVES A vast of transcripts have been found aberrantly expressed in cancers functioning as mechanical factors. The association between the deregulation of long noncoding RNAs (lncRNAs) and clinicopathologic features is one of the most investigated in this field, and many lncRNAs have already been revealed to be potential biomarkers or therapeutic targets. Zinc finger antisense 1 (ZFAS1) has been found one promising lncRNA, initially discovered downregulated in human breast cancer and could regulate alveolar development and epithelial cell differentiation in mice mammary gland, however the subsequent investigation provided inverse outcomes as overexpressed in other human cancers. Further excavation of this transcript indicated that ZFAS1 could function as oncogenic factor via many approaches to contribute to the advance of cancers, including induction of epithelial-mesenchymal transition, sponging microRNAs, destabilization p53 gene and many others. MATERIALS AND METHODS In this work, we summarized current evidence regarding the biological functions and mechanisms of ZFAS1 in human cancers. The related studies were obtained through a systematic search of PubMed, Embase and Cochrane Library. RESULTS LncRNA ZFAS1 is one cancer-implicated product with multiple functional mechanisms, and its potential clinical values is gradually unfolded in many types of cancers, including breast cancer, hepatocellular carcinoma, colorectal cancer, gastric cancer, glioma, ovarian cancer and many others. CONCLUSION The multi-mechanisms of lncRNA ZFAS1 fertilizes its role of potential clinical biomarkers and therapeutic targets.

Long non-coding RNA MIAT in development and disease: a new player in an old game

BackgroundLong non-coding RNAs (lncRNAs), which are a portion of non-protein-coding RNAs (ncRNAs), have manifested a paramount role in the pathophysiology of human diseases, particularly in pathogenesis and progression of disease.Main body of the abstractMyocardial infarction associated transcript (MIAT), which was recently found to demonstrate aberrant expression in various diseases, such as myocardial infarction, schizophrenia, ischemic stroke, diabetic complications, age-related cataract and cancers, is a novel disease-related lncRNA. This work summarize current evidence regarding the biological functions and underlying mechanisms of lncRNA MIAT during disease development.Short conclusionLncRNA MIAT likely represents a feasible cancer biomarker or therapeutic target.