scholarly journals MiRNA-26a Contributes to the Acquisition of Malignant Behaviors of Doctaxel-Resistant Lung Adenocarcinoma Cells through Targeting EZH2

2017 ◽  
Vol 41 (2) ◽  
pp. 583-597 ◽  
Author(s):  
Jing Chen ◽  
Yuejuan Xu ◽  
Leilei Tao ◽  
Yan Pan ◽  
Kai Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Western Blotting ◽  
Human Cancer ◽  
Flow Cytometric Analysis ◽  
Human Lung Cancer ◽  
Luciferase Reporter ◽  
Apoptosis Rate ◽  
Qrt Pcr

Background/Aims: Accumulating evidence revealed that microRNAs (miRNAs) have been demonstrated as critical molecules in tumor development and progression. MiR-26a, located in a fragile chromosomal region associated with various human cancer, has been reported to be involved in regulating various cellular process, such as proliferation, apoptosis and invasion through targeting multiple oncogene. Docetaxel-mediated chemotherapy has been applied in improving the survival and prognosis of patients with advanced lung adenocarcinoma (LAD). However, chemoresistance remains a major impediment to clinical application of this agent. It has been presented that decreased miR-26a expression lead to cisplatin resistance and promoted growth and migration in human lung cancer. Enhancer of zeste homolog 2 (EZH2) is the target of miR-26a. The present study aimed to investigate the function of miR-26a/EZH2 in the acquisition of malignant behaviors of LAD. Methods: MiR-26a and EZH2 expression levels in the dcetaxel-insensitive groups (n = 19) and the docetaxel-sensitive groups (n = 18) were assessed by qRT-PCR. Colony formation assay, flow cytometric analysis, wound healing assay, cell transwell assays and western blotting were performed to assess the effects of miR-26a on proliferation, apoptosis and epithelial-to-mesenchymal (EMT) phenotypes in docetaxel resistant LAD cells in vitro. Xenograft transplantation, immunohistochemistry, tunel assays and western blotting assays were employed to demonstrate the role of miR-26a in docetaxel resistant LAD cells in vivo. The expression level of EZH2 in docetaxel-resistant LAD cells and corresponding parental cells was detected by qRT-PCR and western blotting. The relationship between miR-26a and EZH2 was confirmed by luciferase reporter assay. And rescue assays were performed to further confirm that miRNA-26a contributes to the acquisition of malignant behaviors of docetaxel-resistant LAD cells through targeting EZH2. Results: MiR-26a was significantly down-regulated in the dcetaxel-insensitive groups (n = 19) compared with the docetaxel-sensitive groups (n = 18) assessed by qRT-PCR. MiR-26a decreased the proliferation, increased the apoptosis rate and reversed EMT to MET of docetaxel-resistant LAD cells both in vivo and vitro. EZH2 was confirmed as target of miR-26a. Rescue assays further verified that the function of miR-26a exerts in docetaxel-resistant LAD cells is through targeting EZH2. Conclusions: Our data revealed that overexpression of miR-26a in docetaxel-resistant LAD cells could decrease the proliferation, increase the apoptosis rate and reverse EMT to MET of docetaxel-resistant LAD cells both in vivo and vitro and such function is partially exerted via downregulating EZH2. MiR-26a/EZH2 signal pathway makes contribute to the malignant phenotype of docetaxel-resistant of LAD cells which indicated that miR-26a exerts pivotal functions in the molecular etiology of chemoresistant lung adenocarcinoma.

scholarly journals Long Non-coding RNA TMEM220-AS1 Suppressed Hepatocellular Carcinoma by Regulating the miR-484/MAGI1 Axis as a Competing Endogenous RNA

2021 ◽  
Vol 9 ◽  
Author(s):  
Cong Cao ◽  
Jun Li ◽  
Guangzhi Li ◽  
Gaoyu Hu ◽  
Zhihua Deng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Western Blotting ◽  
Pdz Domain ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Qrt Pcr ◽  
Low Levels ◽  
Hcc Cells

Long non-coding RNAs (lncRNAs) have a considerable regulatory influence on multiple biological processes. Nevertheless, the role of TMEM220-AS1 in hepatocellular carcinoma (HCC) remains unclear. We used The Cancer Genome Atlas (TCGA) database to analyze the differentially expressed lncRNAs. qRT-PCR was used to verify the results for a large population. The in vitro effects of TMEM220-AS1 on HCC cells were determined using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2’-deoxyuridine (EdU), flow cytometry, and Transwell assays in HCC cells. We used qRT-PCR and western blotting to identify the epithelial-mesenchymal transition (EMT). Moreover, we performed bioinformatics analysis, western blotting, dual luciferase reporter gene assay, RNA pull-down, and RNA binding protein immunoprecipitation (RIP) to investigate the underlying molecular mechanisms of TMEM220-AS1 function. Finally, the function of TMEM220-AS1 was verified in vivo. The results showed that TMEM220-AS1 was expressed at considerably low levels in HCC. It was demonstrated that malignant phenotypes and EMT of HCC cells were promoted by the knock down of TMEM220-AS1 both in vivo and in vitro. TMEM220-AS1, which was detected primarily in the cytoplasm, functioned as an miRNA sponge to bind miR-484 and promote the level of membrane-associated guanylate kinase, WW, and PDZ domain containing 1 (MAGI1), thereby curbing the malignant phenotypes of HCC cells. In conclusion, low levels of TMEM220-AS1 promote proliferation and metastasis through the miR-484/MAGI1 axis in HCC.

scholarly journals Hypoxia-Induced miR-137 Inhibition Increased Glioblastoma Multiforme Growth and Chemoresistance Through LRP6

2021 ◽  
Vol 10 ◽  
Author(s):  
Dong-Mei Li ◽  
Qiu-Dan Chen ◽  
Gui-Ning Wei ◽  
Jie Wei ◽  
Jian-Xing Yin ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Cancer Progression ◽  
Flow Cytometric Analysis ◽  
Density Lipoprotein ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Normal Brain ◽  
Qrt Pcr

PurposeGlioblastoma multiforme (GBM) is one of the deadliest tumors, which is involved in numerous dysregulated microRNAs including miR-137. However, the mechanism of how miR-137 suppression associated with cancer progression and chemoresistance still remains to be elucidated.MethodsQuantitative reverse transcriptase-PCR (qRT-PCR), DNA methylation analysis, cell proliferation assay, flow cytometric analysis, invasion assay, in situ tumor formation experiment were performed to test the expression levels and functions of miR-137 in GBM. Bioinformatics analysis, luciferase reporter assay, qRT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry assay were used to identify and verify the target of miR-137.ResultsWe found that miR-137 was downregulated in primary and recurrent GBM compared with normal brain tissues. Overexpression of miR-137 inhibited cell invasion and enhanced cell chemosensitivity to temozolomide (TMZ) by directly targeting low-density lipoprotein receptor-related protein 6 (LRP6) in GBM. Forced expression of LRP6 cDNA without its 3’-UTR region partly restored the effects of miR-137 in vitro and in vivo. Hypoxia-induced miR-137 methylation was responsible for the miR-137 suppression, leading to the cell chemoresistance and poor prognosis of GBM.ConclusionsThese findings demonstrated the detailed molecular mechanism of miR-137 in regulating GBM growth and chemoresistance in hypoxia microenvironment, suggesting the potentiality of miR-137 as a therapeutic target for GBM.

scholarly journals LINC00518 Promotes Cell Proliferation by Regulating the Cell Cycle of Lung Adenocarcinoma Through miR-185-3p Targeting MECP2

2021 ◽  
Vol 11 ◽  
Author(s):  
Xu Han ◽  
Jixiang Wu ◽  
Yajun Zhang ◽  
Jianxiang Song ◽  
Zhan Shi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Lung Adenocarcinoma ◽  
Human Cancer ◽  
Survival Rates ◽  
Bioinformatic Analysis ◽  
Luciferase Reporter

Previous studies have shown that long intergenic non-protein coding RNA 00518 (LINC00518) are essential for the cell growth and metastasis of human cancer. However, the role of LINC00518 in lung adenocarcinoma (LUAD) is still unknown. This research put emphasis on the function of LINC00518 on the cell growth of LUAD. The lncRNA, miRNA and mRNA expression were measured by using qRT-PCR. Protein levels were measured by using Western blotting. CCK-8, colony formation assays and transwell assay were performed to evaluate the cell proliferation ability and invasion. Bioinformatic analysis and luciferase reporter assays were chosen to confirm the mechanism of LINC00518 in LUAD. We found that LINC00518 was highly expressed in LUAD specimens and the high-expression was negatively correlated with the overall survival rates. This finding was also proved in the LUAD cell lines. Through a series of in vitro and in vivo experiments, we proved that LICN00518 promoted the cell growth of LUAD by regulating the cell cycle. Moreover, LICN00518 upregulated the expression of MECP2 by mutagenesis of miR-185-3p. The results suggested that LICN00518 could be used as a survival indicator and potential therapeutic target for LUAD patients.

scholarly journals Honeysuckle Aqueous Extracts Induced let-7a Suppress EV71 Replication and Pathogenesis In Vitro and In Vivo and Is Predicted to Inhibit SARS-CoV-2

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 308
Author(s):  
Ying-Ray Lee ◽  
Chia-Ming Chang ◽  
Yuan-Chieh Yeh ◽  
Chi-Ying F. Huang ◽  
Feng-Mao Lin ◽  
...  
Keyword(s):  
Protein Expression ◽  
Western Blotting ◽  
Expression Profiles ◽  
Plaque Assay ◽  
Virus Titer ◽  
Enterovirus 71 ◽  
Luciferase Reporter ◽  
Pathogen Invasion

Honeysuckle (Lonicera japonica Thunb) is a traditional Chinese medicine (TCM) with an antipathogenic activity. MicroRNAs (miRNAs) are small non-coding RNA molecules that are ubiquitously expressed in cells. Endogenous miRNA may function as an innate response to block pathogen invasion. The miRNA expression profiles of both mice and humans after the ingestion of honeysuckle were obtained. Fifteen overexpressed miRNAs overlapped and were predicted to be capable of targeting three viruses: dengue virus (DENV), enterovirus 71 (EV71) and SARS-CoV-2. Among them, let-7a was examined to be capable of targeting the EV71 RNA genome by reporter assay and Western blotting. Moreover, honeysuckle-induced let-7a suppression of EV71 RNA and protein expression as well as viral replication were investigated both in vitro and in vivo. We demonstrated that let-7a targeted EV71 at the predicted sequences using luciferase reporter plasmids as well as two infectious replicons (pMP4-y-5 and pTOPO-4643). The suppression of EV71 replication and viral load was demonstrated in two cell lines by luciferase activity, RT-PCR, real-time PCR, Western blotting and plaque assay. Furthermore, EV71-infected suckling mice fed honeysuckle extract or inoculated with let-7a showed decreased clinical scores and a prolonged survival time accompanied with decreased viral RNA, protein expression and virus titer. The ingestion of honeysuckle attenuates EV71 replication and related pathogenesis partially through the upregulation of let-7a expression both in vitro and in vivo. Our previous report and the current findings imply that both honeysuckle and upregulated let-7a can execute a suppressive function against the replication of DENV and EV71. Taken together, this evidence indicates that honeysuckle can induce the expression of let-7a and that this miRNA as well as 11 other miRNAs have great potential to prevent and suppress EV71 replication.

scholarly journals METTL14 promotes tumorigenesis by regulating lncRNA OIP5-AS1/miR-98/ADAMTS8 signaling in papillary thyroid cancer

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Xiaoping Zhang ◽  
Dan Li ◽  
Chengyou Jia ◽  
Haidong Cai ◽  
Zhongwei Lv ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Papillary Thyroid ◽  
Qrt Pcr ◽  
The Relationship

Abstract Background Papillary thyroid cancer (PTC) is the most common type of cancer of the endocrine system. Long noncoding RNAs (lncRNAs) are emerging as a novel class of gene expression regulators associated with tumorigenesis. Through preexisting databases available for differentially expressed lncRNAs in PTC, we uncovered that lncRNA OIP5-AS1 was significantly upregulated in PTC tissues. However, the function and the underlying mechanism of OIP5-AS1 in PTC are poorly understood. Methods Expression of lncRNA OIP5-AS1 and miR-98 in PTC tissue and cells were measured by quantitative real-time PCR (qRT-PCR). And expression of METTL14 and ADAMTS8 in PTC tissue and cells were measured by qRT-PCR and western blot. The biological functions of METTL14, OIP5-AS1, and ADAMTS8 were examined using MTT, colony formation, transwell, and wound healing assays in PTC cells. The relationship between METTL14 and OIP5-AS1 were evaluated using RNA immunoprecipitation (RIP) and RNA pull down assay. And the relationship between miR-98 and ADAMTS8 were examined by luciferase reporter assay. For in vivo experiments, a xenograft model was used to investigate the effects of OIP5-AS1 and ADAMTS8 in PTC. Results Functional validation revealed that OIP5-AS1 overexpression promotes PTC cell proliferation, migration/invasion in vitro and in vivo, while OIP5-AS1 knockdown shows an opposite effect. Mechanistically, OIP5-AS1 acts as a target of miR-98, which activates ADAMTS8. OIP5-AS1 promotes PTC cell progression through miR-98/ADAMTS8 and EGFR, MEK/ERK pathways. Furthermore, RIP and RNA pull down assays identified OIP5-AS1 as the downstream target of METTL14. Overexpression of METTL14 suppresses PTC cell proliferation and migration/invasion through inhibiting OIP5-AS1 expression and regulating EGFR, MEK/ERK pathways. Conclusions Collectively, our findings demonstrate that OIP5-AS1 is a METTL14-regulated lncRNA that plays an important role in PTC progression and offers new insights into the regulatory mechanisms underlying PTC development.

scholarly journals CircKEAP1 Suppresses the Progression of Lung Adenocarcinoma via the miR-141-3p/KEAP1/NRF2 Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Yanbo Wang ◽  
Fenghai Ren ◽  
Dawei Sun ◽  
Jing Liu ◽  
BenKun Liu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Lung Adenocarcinoma ◽  
Expression Profiles ◽  
Luciferase Reporter ◽  
Tumor Tissues ◽  
Tumor Progress ◽  
Rna Immunoprecipitation ◽  
Novel Method

BackgroundLung cancer is the leading cause of death from cancer, and lung adenocarcinoma (LUAD) is the most common form. Despite the great advances that has been made in the diagnosis and treatment for LUAD, the pathogenesis of LUAD remains unclear. In this study, we aimed to identify the function of circKEAP1 derived from the exon of KEAP1 in LUAD.MethodsThe expression profiles of circRNAs in LUAD tissues and adjacent non-tumor tissues were analyzed by Agilent Arraystar Human CircRNA microarray. The levels and prognostic values of circKEAP1 in tissues and cancer cell lines were determined by quantitative real-time PCR (qRT-PCR). Subsequently, the effects of circKEAP1 on tumor growth were investigated by functional experiments in vitro and in vivo. Mechanistically, the dual luciferase reporter assay, RNA pull-down, and RNA immunoprecipitation experiments were performed to confirm the interaction between circKEAP1 and miR-141-3p in LUAD.ResultsWe found circKEAP1 was significantly downregulated in LUAD tissues and repressed tumor growth both in vitro and in vivo. Mechanistically, circKEAP1 competitively binds to miR-141-3p and relive miR-141-3p repression for its host gene, which activated the KEAP1/NRF2 signal pathway, and finally suppresses the tumor progress. Our findings suggest that circKEAP1 inhibits LUAD progression through circKEAP1/miR-141-3p/KEAP1 axis and it may serve as a novel method for the treatment of LUAD.

scholarly journals MiR-203 Determines Poor Outcome and Suppresses Tumor Growth by Targeting TBK1 in Osteosarcoma

2015 ◽  
Vol 37 (5) ◽  
pp. 1956-1966 ◽  
Author(s):  
Shiping Liu ◽  
Peng Feng
Keyword(s):  
Cell Growth ◽  
Cell Lines ◽  
Cancer Progression ◽  
Human Cancer ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Poor Overall Survival ◽  
Gene Assay

Background/Aims: Increasing evidence has shown that miR-203 plays important role in human cancer progression. However, little is known about the function of miR-203 in osteosarcoma (OS). Methods: The expression of miR-203 in OS tissues and cell lines were examined by qRT-PCR. The biological role of miR-20 in OS cell proliferation was examined in vitro and in vivo. The targets of miR-203 were identified by a luciferase reporter gene assay. Results: miR-203 was down regulated in OS tissues and cell lines; decreased miR-203 was associated with a poor overall survival in OS patients. Restoration of miR-203 expression reduced cell growth in vitro and suppressed tumorigenicity in vivo. In contrast, inhibition of miR-203 stimulated OS cell growth both in vitro and in vivo. In addition, TANK binding kinase 1 (TBK1) was identified as a direct target of miR-203; overexpression of TBK1 partly reversed the suppressive effects of miR-203. Furthermore, TBK1 was found up-regulated and inversely correlated with miR-203 in OS tissues. Conclusion: Taken together, these findings suggest that miR-203 acts as a tumor suppressor via regulation of TBK1 expression in OS progression, and miR-203 may be a promising therapeutic target for OS.

scholarly journals TP53-Activated lncRNA GHRLOS Regulates Cell Proliferation, Invasion, and Apoptosis of Non-Small Cell Lung Cancer by Modulating the miR-346/APC Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ke Ren ◽  
Jinghui Sun ◽  
Lingling Liu ◽  
Yuping Yang ◽  
Honghui Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Qrt Pcr ◽  
Proliferation And Invasion

Non-small cell lung cancer (NSCLC) is the main type of lung cancer with high mortality worldwide. To improve NSCLC therapy, the exploration of molecular mechanisms involved in NSCLC progression and identification of their potential therapy targeting is important. Long noncoding RNAs (lncRNAs) have shown important roles in regulating various tumors progression, including NSCLC. We found lncRNA GHRLOS was decreased in NSCLC cell lines and tissues which correlated with poor prognosis of NSCLC patients. However, the role and underlying mechanisms of lncRNA GHRLOS in NSCLC progression remains elusive. The expression of lncRNA GHRLOS was examined in NSCLC cell lines and biopsy specimens of patients with NSCLC by quantitative real time polymerase chain reaction (qRT-PCR). The effects of GHRLOS on proliferation, invasion and apoptosis of NSCLC cells were determined by both in vitro and in vivo experiments. The interaction between GHRLOS and TP53 was determined by dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) combined with qRT-PCR analysis. RNA immunoprecipitation (RIP) was conducted to validate the binding between GHRLOS and microRNA-346 (miR-346). Dual-luciferase reporter assays were also carried out to reveal the interaction between miR-346 and the 3’ untranslated region (3’UTR) of adenomatous polyposis coli (APC) mRNA.Our data demonstrated that overexpression of lncRNA GHRLOS suppressed cancer cell proliferation and invasion as well as promoted cell apoptosis by regulating the expression of CDK2, PCNA, E-cadherin, N-cadherin, Bax, and Bcl-2 in NSCLC cells. Moreover, lncRNA GHRLOS was upregulated by the binding of TP53 to the GHRLOS promoter. The binding target of lncRNA GHRLOS was identified to be miR-346. Impressively, overexpression of miR-346 promoted cell proliferation and invasion, as well as inhibited cell apoptosis, however, these effects can be blocked by overexpression of lncRNA GHRLOS both in vitro and in vivo. In summary, this study reveals lncRNA GHRLOS, upregulated by TP53, acts as a molecule sponge of miR-346 to cooperatively modulates expression of APC, a miR-346 target, and potentially inhibits NSCLC progression via TP53/lncRNA GHRLOS/miR-346/APC axis, which represents a novel pathway that could be useful in targeted therapy against NSCLC.

scholarly journals The Long Non-coding RNA LINC01133 Promotes Hepatocellular Carcinoma Progression by Sponging miR-199a-5p and Activating Annexin A2

2020 ◽  
Author(s):  
Dan Yin ◽  
Zhi-Qiang Hu ◽  
Chu-Bin Luo ◽  
Xiao-Yi Wang ◽  
Hao-Yang Xin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Western Blot ◽  
Copy Number ◽  
Poor Prognosis ◽  
Annexin A2 ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Qrt Pcr

Abstract Background: Long non-coding RNAs (lncRNAs) have been found to be functionally associated with cancer development and progression. Although copy number variations (CNVs) are common in hepatocellular carcinoma (HCC), little is known about how CNVs in lncRNAs affect HCC progression and recurrence.Methods: We analyzed the whole genome sequencing (WGS) data of matched cancerous and non-cancerous liver samples from 49 patients with HCC to identify lncRNAs with CNVs. The results were validated in another cohort of 238 paired HCC and non-tumor samples by TaqMan copy number assay. Kaplan-Meier analysis and the log-rank test were performed to determine the prognostic value of CNVs in lincRNAs. Loss- and gain-of-function studies were conducted to determine the biological functions of LINC01133 in vitro and in vivo. The competing endogenous RNAs (ceRNAs) mechanism was clarified by microRNA sequencing (miR-seq), quantitative real-time PCR (qRT-PCR), western blot, and dual-luciferase reporter analyses. The protein binding mechanism was confirmed by RNA pull-down, RNA immunoprecipitation (RIP), qRT-PCR, and western blot analyses.Results: Genomic copy number of LINC01133 was increased in HCC, which is positively related with the elevated expression of LINC01133. Increased copy number of LINC01133 predicted the poor prognosis in HCC patients. LINC01133 overexpression promoted proliferation, colony formation, migration, and invasion in vitro, and facilitated tumor growth and lung metastasis in vivo, whereas LINC01133 knockdown had the opposite effects. Mechanistically, LINC01133 acted as a sponge of miR-199a-5p, resulting in enhanced expression of SNAI1, which induced epithelial-mesenchymal transition (EMT) in HCC cells. In addition, LINC01133 interacted with Annexin A2 (ANXA2) to activate ANXA2/STAT3 signaling pathway.Conclusions: LINC01133 promotes HCC progression by sponging miR-199a-5p and interacting with ANXA2. LINC01133 CNV gain is predictive of poor prognosis in HCC patients undergoing curative resection.

scholarly journals Linc00473 potentiates cholangiocarcinoma progression by modulation of DDX5 expression via miR-506 regulation

2020 ◽  
Author(s):  
Lining Huang ◽  
Xingming Jiang ◽  
Zhenglong Li ◽  
Jinglin Li ◽  
Xuan Lin ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Qrt Pcr ◽  
Competitive Endogenous Rnas ◽  
Rna Immunoprecipitation ◽  
Underlying Mechanisms

Abstract Background: Cholangiocarcinoma (CCA) is a mortal cancer with high mortality, whereas the function and mechanism of occurrence and progression of CCA are still mysterious. Long non-coding RNAs (lncRNAs) could function as important regulators in carcinogenesis and cancer progression. Growing evidences have indicated that the novel lncRNA linc00473 plays an important role in cancer progression and metastasis. However, its function and molecular mechanism in CCA remain unknown. Methods: The linc00473 expression in CCA tissues and cell lines was analyzed using qRT-PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of linc00473 both in vitro and in vivo. Insights into the underlying mechanisms of competitive endogenous RNAs (ceRNAs) were determined by bioinformatics analysis, dual-luciferase reporter assays, qRT-PCR arrays, RNA immunoprecipitation (RIP) and rescue experiments. Results: Linc00473 was highly expressed in CCA tissues and cell lines. Linc00473 knockdown inhibited CCA growth and metastasis. Furthermore, linc00473 acted as miR-506 sponge and regulated its target gene DDX5 expression. Rescue assays verified that linc00473 modulated the tumorigenesis of CCA by regulating miR-506. Conclusions: The data indicated that linc00473 played an oncogenic role in CCA growth and metastasis, and could serve as a novel molecular target for treating CCA.

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