scholarly journals LncRNA RHPN1-AS1 Promotes Cell Proliferation, Migration and Invasion Through Targeting miR-7-5p and Activating PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma

2020 ◽  
Vol 19 ◽  
pp. 153303382095702
Author(s):  
Xue-zhen Song ◽  
Xiao-ning Ren ◽  
Xiao-jun Xu ◽  
Xiao-xuan Ruan ◽  
Yi-li Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Molecular Mechanism ◽  
Cancer Progression ◽  
Cell Clone ◽  
Mtor Pathway ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gene Assay ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is a severe disease with high mortality in the world. Emerging evidence has suggested that lncRNAs play an important role in cancer progression, including HCC. This study aimed to comprehensively investigate the effect of lncRNA RHPN1 antisense RNA 1 (RHPN1-AS1) on HCC and its underlying molecular mechanism. In this study, we evaluated the expressions of lncRNA RHPN1-AS1 and miR-7-5p by qRT-RCR in both HCC tissue and HCC cells. Our findings showed that lncRNA RHPN1-AS1 was upregulated in HCC tissue and HCC cells, while miR-7-5p was downregulated. LncRNA RHPN1-AS1 expression in HCC patients was closely related to vascular invasion, tumor-node-metastasis (TNM) stage and barcelona clinic liver cancer (BCLC) stage. Furthermore, we quantified cell clone-formation ability, proliferation, migration and invasion of HCCLM3 and MHCC97 H cells using several assays (colony formation assay, 5-Ethynyl-2′-deoxyuridine (EdU) assay and transwell assay, respectively). Functional experiments confirmed that silencing lncRNA RHPN1-AS1 inhibited cell proliferation, migration and invasion in HCCLM3 and MHCC97 H cells. After that, bioinformatics analysis, dual luciferase reporter gene assay, qRT-PCR and western blot were used to investigate the molecular mechanism of lncRNA RHPN1-AS1 on HCC. Mechanistically, the rescue experiments demonstrated that miR-7-5p inhibitor reversed the inhibition effect of silencing lncRNA RHPN1-AS1 on HCCLM3 cells proliferation, migration and invasion. Moreover, silencing lncRNA RHPN1-AS1 also inhibited the activation of PI3K/AKT/mTOR pathway. Taken together our findings demonstrated that lncRNA RHPN1-AS1 could facilitate cell proliferation, migration and invasion via targeting miR-7-5p and activating PI3K/AKT/mTOR pathway in HCC.

scholarly journals Circular RNA hsa_circ_101555 promotes hepatocellular carcinoma cell proliferation and migration by sponging miR-145-5p and regulating CDCA3 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Xiaoguang Gu ◽  
Jianan Zhang ◽  
Yajuan Ran ◽  
Hena Pan ◽  
JinHong Jia ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Biological Effects ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Casein Kinase 1 ◽  
Mouse Xenograft Model ◽  
Hcc Cells

AbstractCircular RNAs have been reported to play significant roles in regulating pathophysiological processes while also guiding clinical diagnosis and treatment of hepatocellular carcinoma (HCC). However, only a few circRNAs have been identified thus far. Herein, we investigated the role of a specific closed-loop structure of hsa_circ_101555 that was generated by back-splicing of the host gene casein kinase 1 gamma 1 (CSNK1G1) in the development and proliferation of HCC. We investigated the expression of Hsa_circ_101555 in HCC and normal tissues using bioinformatics. The expression level of hsa_circ_101555 was further detected by fluorescence in situ hybridization and qRT-PCR in ten HCC patients. Transwell, migration, WST-1 assays, and colony formation assays were used to evaluate the role of hsa_circ_101555 in HCC development and proliferation. The regulatory mechanisms of hsa_circ_101555 in miR-145-5p and CDCA3 were determined by dual luciferase reporter assay. A mouse xenograft model was also used to determine the effect of hsa_circ_101555 on HCC growth in vivo. hsa_circ_101555 showed greater stability than the linear RNA; while in vitro and in vivo results demonstrated that hsa_circ_101555 silencing significantly suppressed cell proliferation, migration, and invasion of HCC cells. Rescue experiments further demonstrated that suppression of miR-145-5p significantly attenuated the biological effects of hsa_circ_101555 knockdown in HCC cells. We also identified a putative oncogene CDCA3 as a potential miR-145-5p target. Thus, our results demonstrated that hsa_circ_101555 might function as a competing endogenous RNA of miR-145-5p to upregulate CDCA3 expression in HCC. These findings suggest that hsa_circ_101555 may be a potential therapeutic target for patients with HCC.

scholarly journals Long non-coding RNA TUG1 promotes cell progression in hepatocellular carcinoma via regulating miR-216b-5p/DLX2 axis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Qun Dai ◽  
Jingyi Deng ◽  
Jinrong Zhou ◽  
Zhuhong Wang ◽  
Xiao-feng Yuan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Marked Rise ◽  
Hcc Cells

Abstract Background Accumulating evidence indicates that the long noncoding RNA taurine upregulated gene 1(TUG1) plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of TUG1 in hepatocellular carcinoma (HCC) remain largely unknown. Methods The expressions of TUG1, microRNA-216b-5p and distal-less homeobox 2 (DLX2) were detected by Quantitative real-time polymerase chain reaction (qRT-PCR). The target relationships were predicted by StarBase v.2.0 or TargetScan and confirmed by dual-luciferase reporter assay. The cell growth, apoptosis, migration and invasion were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Flow cytometry and Transwell assays, respectively. All protein expression levels were detected by western blot. Tumor xenografts were implemented to explore the role of TUG1 in vivo. Results We found that there was a marked rise in TUG1 expression in HCC tissues and cells, and knockdown of TUG1 repressed the growth and metastasis and promoted apoptosis of HCC cells. In particular, TUG1 could act as a ceRNA, effectively becoming a sink for miR-216b-5p to fortify the expression of DLX2. Additionally, repression of TUG1 impared the progression of HCC cells by inhibiting DLX2 expression via sponging miR-216b-5p in vitro. More importantly, TUG1 knockdown inhibited HCC tumor growth in vivo through upregulating miR-216b-5p via inactivation of the DLX2. Conclusion TUG1 interacting with miR-216b-5p contributed to proliferation, metastasis, tumorigenesis and retarded apoptosis by activation of DLX2 in HCC.

scholarly journals Tumor-Suppressive Role of microRNA-202-3p in Hepatocellular Carcinoma Through the KDM3A/HOXA1/MEIS3 Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Yijie Zhang ◽  
Qi Pan ◽  
Zigong Shao
Keyword(s):  
Hepatocellular Carcinoma ◽  
Normal Liver ◽  
Global Scale ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
Patient Prognosis ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) represents a malignant tumor predominantly arising in the setting of cirrhosis and is the third most common cause of cancer-associated death on a global scale. The heterogeneous nature of HCC and limited well-recognized biomarkers may contribute to poor patient prognosis and treatment failure. In this study, we identified expression pattern of microRNA-202-3p (miR-202-3p) in HCC and characterized its functional role as well as related mechanisms. First, we collected 50 HCC tissues and 38 normal liver tissues, and after bioinformatics prediction, the expression of miR-202-3p and KDM3A was determined in the tissues. We found lowly expressed miR-202-3p and overexpressed KDM3A in HCC tissues. Then, dual-luciferase reporter gene assay was employed to test the presence of miR-202-3p binding sites in the 3’UTR of KDM3A and chromatin immunoprecipitation (ChIP) assay to homeobox A1 (HOXA1) interaction with KDM3A and MEIS3. It has been confirmed that miR-202-3p negatively regulated KDM3A responsible for increasing the expression of HOXA1 by eliminating the histone H3 lysine 9 (H3K9)me2 in HCC cells. HOXA1 could evidently increase H3K4me1 and H3K27ac enrichment in the MEIS3 enhancer region and enhance the expression of MEIS3. Functional assays were also performed with the results showing that upregulated miR-202-3p or downregulated KDM3A retarded HCC cell viability, migration, and invasion. In addition, HepG2 cells were xenografted into nude mice, and we demonstrated that upregulated miR-202-3p reduced the growth of human HCC cells in vivo. Taken together, the present study elicits a novel miR-202-3p/KDM3A/HOXA1/MEIS3 pathway in HCC, potentiating an exquisite therapeutic target for HCC.

scholarly journals Hsa_circ_0000520 is Involved in Breast Cancer Progression by Targeting miR-542-3p/S1PR1 Axis

2021 ◽  
Author(s):  
Jianjie Zhao ◽  
Xueqin Wang ◽  
Juan Jiang ◽  
Yao Ding ◽  
qinan wu
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cell Multiplication ◽  
Sample Collection ◽  
Luciferase Reporter Gene ◽  
Gene Assay

Abstract Background: CircRNAs feature prominently in breast cancer (BC) progression. This study was intended to investigate the role of hsa_circ_0000520 in BC progression.Methods: After the sample collection, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted for quantifying the expressions of circ_0000520, miR-542-3p, and sphingosine-1-phosphate receptor 1 (S1PR1) mRNA. 5‐Ethynyl‐2′‐Deoxyuridine (EdU) and cell counting kit-8 (CCK-8) assays were used for measuring cell proliferation. Transwell assays were employed to detect cell migration and invasion. Western blotting was utilized for analyzing S1PR1 protein expression. Dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay were used to delve into the targeting relationship between circ_0000520 and miR-542-3p.Results: Circ_0000520 expression was markedly elevated in BC cell lines and tissues, and knockdown of circ_0000520 could inhibit BC cell multiplication, migration, and invasion. Circ_0000520 could target miR-542-3p to negatively regulate S1PR1 expression. S1PR1 overexpression plasmid could counteract the inhibitory effects of circ_0000520 knockdown on BC cell proliferation, migration, and invasion.Conclusion: Circ_0000520, as a cancer-promoting circRNA, participates in BC progression by regulating miR-542-3p/S1PR1 axis.

scholarly journals CircRNA LRIG3 knockdown inhibits hepatocellular carcinoma progression by regulating miR-223-3p and MAPK/ERK pathway

2021 ◽  
Author(s):  
Hui Sun ◽  
Junwei Zhai ◽  
Li Zhang ◽  
Yingnan Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Mitogen Activated Protein Kinase ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Erk Pathway ◽  
Mitogen Activated Protein ◽  
Hcc Cells

IntroductionEmerging evidence suggests that circular RNAs (circRNAs) play critical roles in tumorigenesis. However, the roles and molecular mechanisms of circRNA leucine-rich repeat immunoglobulin domain-containing protein 3 (circ_LRIG3) in hepatocellular carcinoma (HCC) has not been investigated.Material and methodsThe expression levels of circ_LRIG3, miR-223-3p, and mitogen-activated protein kinase kinase 6 (MAP2K6) were determined by qRT-PCR. Flow cytometry was applied to determine the cell cycle distribution and apoptosis. Cell proliferation, migration and invasion were assessed by MTT, colony formation, and transwell assays. Western blot assay was employed to measure the protein levels of the snail, E-cadherin, MAP2K6, mitogen-activated protein kinase (MAPK), phospho-MAPK (p-MAPK), extracellular signal-regulated kinases (ERKs), and phospho-ERKs (p- ERKs). The relationship between miR-223-3p and circ_LRIG3 or MAP2K6 was predicted by bioinformatics tools and verified by dual-luciferase reporter assay. A xenograft tumor model was established to confirm the functions of circ_LRIG3 in vivo.ResultsCirc_LRIG3 and MAP2K6 expression were enhanced while miR-223-3p abundance was reduced in HCC tissues and cells. Knockdown of circ_LRIG3 inhibited cell proliferation, metastasis, and increasing apoptosis. MiR-223-3p was a target of circ_LRIG3, and its downregulation reversed the inhibitory effect of circ_LRIG3 knockdown on the progression of HCC cells. Moreover, MAP2K6 could bind to miR-223-3p, and MAP2K6 upregulation also abolished the suppressive impact of circ_LRIG3 interference on progression of HCC cells. Additionally, the silence of circ_LRIG3 suppressed the activation of the MAPK/ERK pathway and tumor growth by upregulating miR-223-3p and downregulating MAP2K6.ConclusionsCirc_LRIG3 knockdown inhibited HCC progression through regulating miR-223-3p/MAP2K6 axis and inactivating MAPK/ERK pathway.

MiR-3144 Suppresses Cell Proliferation, Migration, Invasion and Promotes Cell Apoptosis by Targeting Steap4 in Hepatocellular Carcinoma

2019 ◽  
Vol 9 (8) ◽  
pp. 1100-1107
Author(s):  
Qiuyuan Shi ◽  
Dandan Shen ◽  
Yuanjiang Shang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Apoptotic Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Novel Target ◽  
Hcc Cells

Background: MicroRNAs (miRNAs) play important roles in the carcinogenesis and progression of hepatocellular carcinoma (HCC). Previous studies have shown that miR-3144 is down-regulated in HCC tissues. The present study investigated the expression and biological roles, underlying mechanisms of miR-3144 in HCC cell lines. Methods and material: RT-qPCR analysis was performed to detect miR-3144 expression in the HCC cell lines and normal hepatic cell line. CCK-8 assay showed that the effect of miR-3144 expression on cell proliferation. Using wound healing assay and Transwell assay to detect the effect of miR-3144 on cell invasion and migration of HCC. Flow cytometry assay showed that miR-3144 induced apoptotic cell death in the SK-HEP-1 cells. Luciferase reporter assay was performed to evaluate the interaction between miR-3144 and the Steap4 3′-UTR. Western blotting assay were performed to investigate the effect of miR-3144 expression on the expression of CDK2, cyclinE1, p21, MMP2, MMP9 and Steap4. Results: MiR-3144 expression was downregulated in HCC cell lines. MiR-3144 overexpression inhibited the proliferation of HCC cells via regulating CDK2, cyclinE1 and p21 in SK-HEP-1 cells. MiR-3144 suppressed the migration and invasion of HCC cells via decreasing the MMP2 and MMP9. Further, miR-3144 promotes cell apoptosis of HCC. Moreover, miR-3144 negatively regulated Steap4 expression by directly binding to the 3′-UTR of Steap4 mRNA. Conclusion: Our results suggested that miR-3144 may be a novel target for future HCC therapy.

miR-96 targets SOX6 and promotes proliferation, migration, and invasion of hepatocellular carcinoma

2018 ◽  
Vol 96 (3) ◽  
pp. 365-371 ◽  
Author(s):  
Zhengwei Li ◽  
Ying Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Biological Functions ◽  
Promote Cell Proliferation ◽  
Protein Expressions ◽  
Reporter Assays ◽  
Hcc Cells

Recent research suggested that microRNA 96 (miR-96) might function as an oncogene in several types of cancers. Therefore, the purpose of this study was to probe into the mechanism of miR-96 in hepatocellular carcinoma (HCC) cells. HCC tissues and non-tumorous tissues, HCC cell lines, and healthy cell lines were all involved in this study. Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect miR-96 and SOX6 mRNA and protein expressions. The direct regulation of miR96 on SOX6 was confirmed by luciferase reporter assays. Cell proliferation and growth were determined by MTT (3-(4,5-dimethyl–2-thiazolyl)–2,5-diphenyl–2-H-tetrazolium bromide) assay and colony formation assay. Wound healing and transwell assay were employed for migration and invasion analyses. Finally, SPSS 21.0 and GraphPad 7.0 were applied for statistical analyses. In HCC tissues, miR-96 was highly expressed while SOX6 was lowly expressed. The overexpression of miR-96 reversely inhibited the expression of SOX6, contributing to the promotion of the biological functions of HCC cells. miR-96 could promote cell proliferation, migration, and invasion in HCC by targeting SOX6.

scholarly journals CircRNA LRIG3 knockdown inhibits the progression of hepatocellular carcinoma by regulating miR-223-3p/MAP2K6 axis and inactivating MAPK/ERK pathway

2020 ◽  
Author(s):  
Hui Sun ◽  
Junwei Zhai ◽  
Li Zhang ◽  
Yingnan Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cell Cycle Distribution ◽  
Erk Pathway ◽  
Mitogen Activated Protein ◽  
Hcc Cells

Abstract Background: Emerging evidence suggests that circular RNAs (circRNAs) play critical roles in tumorigenesis. However, the roles and molecular mechanism of circRNA leucine-rich repeat immunoglobulin domain-containing protein 3 (circ_LRIG3) in hepatocellular carcinoma (HCC) have not been investigated.Methods: The expression levels of circ_LRIG3, microRNA-223-3p (miR-223-3p), and mitogen-activated protein kinase kinase 6 (MAP2K6) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Flow cytometry was applied to determine the cell cycle distribution and cell apoptosis. Cell proliferation, migration and invasion were assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and transwell assay, respectively. Western blot assay was employed to measure the protein levels of snail, E-cadherin, MAP2K6, mitogen-activated protein kinase (MAPK), phospho-MAPK (p-MAPK), extracellular signal-regulated kinases (ERKs), and phospho-ERKs (p-ERKs). The relationship between miR-223-3p and circ_LRIG3 or MAP2K6 was predicted by bioinformatics tools and verified by dual-luciferase reporter assay. A xenograft tumor model was established to confirm the functions of circ_LRIG3 in vivo.Results: Circ_LRIG3 and MAP2K6 expression were enhanced while miR-223-3p abundance was reduced in HCC tissues and cells. Knockdown of circ_LRIG3 inhibited the progression of HCC cells via reducing cell proliferation, metastasis and increasing apoptosis. MiR-223-3p was a target of circ_LRIG3 and its downregulation reversed the inhibitory effect of circ_LRIG3 knockdown on progression of HCC cells. Moreover, MAP2K6 could bind to miR-223-3p, and MAP2K6 upregulation also abolished the suppressive impact of circ_LRIG3 interference on progression of HCC cells. Additionally, silence of circ_LRIG3 suppressed the activation of MAPK/ERK pathway and tumor growth by upregulating miR-223-3p and downregulating MAP2K6.Conclusion: Circ_LRIG3 knockdown inhibited HCC progression through regulating miR-223-3p/MAP2K6 axis and inactivating MAPK/ERK pathway, providing a potential therapeutic approach for patients with HCC.

scholarly journals Upregulation of miR-1266-5p serves as a prognostic biomarker of hepatocellular carcinoma and facilitates tumor cell proliferation, migration and invasion

2021 ◽  
Author(s):  
Yan Su ◽  
Ruizhu Xie ◽  
Qinyan Xu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Tnm Stage ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Elevated Expression ◽  
Hcc Cells

Objective: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. This study aimed to analyze the prognostic value of microRNA-1266-5p (miR-1266-5p) in HCC patients and investigate its biological function in HCC progression. Methods: The expression of miR-1266-5p in tissues and cells was measured by quantitative real-time PCR (qRT-PCR). Cell counting kit-8 (CCK-8) assay was used to detect HCC cell proliferation. Transwell assay was performed to evaluate the migration and invasion of HCC cells. Kaplan-Meier methods and Cox regression analysis were used to assess the prognostic value of miR-1266-5p in HCC patients. The relationship between miR-1266-5p and DAB2IP was evaluated by luciferase reporter assay. Results: Relative expression of miR-1266-5p in tumor tissues, tissues from patients with advanced TNM stage (III–IV) and HCC cells was increased compared with that in corresponding control group. MiR-1266-5p expression was significantly associated with tumor size and TNM stage in HCC patients. Elevated expression of miR-1266-5p was associated with poor prognosis of HCC patients and served as an independent prognostic factor for HCC patients. Overexpression of miR-1266-5p significantly promoted, while miR-1266-5p knockdown significantly inhibited the proliferation, migration and invasion of HCC cells. DAB2IP could directly bind to the miR-1266-5p. Conclusion: Our findings indicated that elevated expression of miR-1266-5p can predict the poor prognosis of HCC patients, and promotes the proliferation, migration and invasion of HCC cells. Therefore, we predict that miR-1266-5p may be a novel biomarker and therapeutic target for the treatment of HCC.

scholarly journals HOXA-AS2 Promotes Proliferation and Induces Epithelial-Mesenchymal Transition via the miR-520c-3p/GPC3 Axis in Hepatocellular Carcinoma

2018 ◽  
Vol 50 (6) ◽  
pp. 2124-2138 ◽  
Author(s):  
Ying Zhang ◽  
Jianliang Xu ◽  
Shaoquan Zhang ◽  
Jun An ◽  
Jin Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Reporter Assay ◽  
Online Programs ◽  
Hcc Cells

Background/Aims: Previous studies have demonstrated that long non-coding RNAs (lncRNAs) may play critical roles in cancer biology, including Hepatocellular carcinoma (HCC). The HOXA cluster antisense RNA2 (HOXA-AS2) lncRNA plays an important role in carcinogenesis, however, the underlying role of HOXA-AS2 in HCC remains unknown. The present study examined the effects of HOXA-AS2 on the progression of HCC, and explored the underlying molecular mechanisms. Methods: Quantitative real-time PCR was used to detect HOXA-AS2 expression in HCC tissues and cell lines. Furthermore, the effects of HOXA-AS2 silencing and overexpression on cell proliferation, cell cycle, apoptosis, migration, and invasion were assessed in HCC in vitro and in vivo. Furthermore, bioinformatics online programs predicted and luciferase reporter assay were used to validate the association of HOXA-AS2 and miR-520c-3p in HCC cells. Results: We observed that HOXA-AS2 was up-regulated in HCC tissues and cell lines. In vitro experiments revealed that HOXA-AS2 knockdown significantly inhibited HCC cells proliferation by causing G1 arrest and promoting apoptosis, whereas HOXA-AS2 overexpression promoted cell growth. Further functional assays indicated that HOXA-AS2 significantly promoted HCC cell migration and invasion by promoting EMT. Bioinformatics online programs predicted that HOXA-AS2 sponge miR-520c-3p at 3’-UTR with complementary binding sites, which was validated using luciferase reporter assay. HOXA-AS2 could negatively regulate the expression of miR-520c-3p in HCC cells. MiR-520c-3p was down-regulated and inversely correlated with HOXA-AS2 expression in HCC tissues. miR-520c-3p suppressed cell proliferation, invasion and migration in HCC cells, and enforced expression of miR-520c-3p attenuated the oncogenic effects of HOXA-AS2 in HCC cells. By bioinformatic analysis and dual-luciferase reporter assay, we found that miR-223-3p directly targeted the 3’-untranslated region (UTR) of Glypican-3 (GPC3), one of the key players in HCC. GPC3 was up-regulated in HCC tissues, and was negatively correlated with miR-520c-3p expression and positively correlated with HOXA-AS2 expression. Conclusion: In summary, our results suggested that the HOXA-AS2/miR-520c-3p/GPC3 axis may play an important role in the regulation of PTC progression, which could serve as a biomarker and therapeutic target for HCC.

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