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

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.

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Liver X receptor inhibits the growth of hepatocellular carcinoma cells via regulating HULC/miR-134-5p/FOXM1 axis

10.21203/rs.2.22627/v1 ◽

2020 ◽

Author(s):

Yan Zhang ◽

Jintao He ◽

Teng Yang ◽

Wenhui He ◽

Shan Jiang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cyclin D1 ◽

Gene Promoter ◽

Liver X Receptor ◽

Cell Counting ◽

Luciferase Reporter ◽

In Vivo Experiments ◽

Hcc Cells

Abstract Background Highly upregulated in liver cancer (HULC), the specifically overexpressed long non-coding RNA (lncRNA) in human hepatocellular carcinoma (HCC), can promote the growth and metastasis of HCC cells. Therefore, it will be benefit to HCC treatment by effectively downregulating HULC. Liver X receptor (LXR), a member of nuclear receptor superfamily, exerts anti-tumor effects on various human malignancies including HCC. However, it is unclear whether the anti-HCC function of LXR is involved in the regulation of HULC. Methods Quantitative real-time PCR and Western blot were used to separately examine RNA and protein levels in HCC cells. Cell counting kit-8 assay was used to detect the growth of HCC cells in vitro . Dual-luciferase reporter assays were performed to analyze the regulation of forkhead box M1 (FOXM1) by miR-134-5p and the regulation of miR-134-5p by HULC. Xenograft models were engaged to evaluate the growth of HCC cells in vivo . Results In this study, we found that activation of LXR could inhibit the growth of HCC cells by downregulating HULC. Mechanistically, LXR decreased HULC via suppressing its gene promoter activity. Moreover, HULC and FOXM1 were highly expressed while miR-134-5p was lowly expressed in HCC tissues, and the level of HULC was positively correlated with that of FOXM1 while negatively correlated with that of miR-134-5p. Additionally, miR-134-5p downregulated FOXM1 by targeting 3′-untranslated region (UTR) of its mRNA, and HULC upregulated FOXM1 and its downstream target molecule cyclin D1 through sequestrating miR-134-5p. Furthermore, activation of LXR increased miR-134-5p while decreased FOXM1 by reducing HULC in HCC cells. The in vivo experiments showed that activation of LXR repressed the growth of HCC xenografts, and decreased HULC, FOXM1 and cyclin D1 while increased miR-134-5p in the xenografts. Conclusions Our results for the first time reveal that LXR can inhibit the growth of HCC cells by regulating HULC/miR-134-5p/FOXM1 axis. The novel pathway LXR/HULC/miR-134-5p/FOXM1 may serve as a promising target in HCC treatment.

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

10.21203/rs.3.rs-88668/v1 ◽

2020 ◽

Author(s):

Cong Cao ◽

Jun Li ◽

Guangzhi Li ◽

Gaoyu Hu ◽

Zhihua Deng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Western Blot ◽

Luciferase Reporter ◽

Mesenchymal Transition ◽

Qrt Pcr ◽

Non Coding Rna ◽

Gene Assay ◽

Hcc Cells

Abstract BackgroundLong non-coding RNA has a considerable regulative influence in multiple biological processes. Nevertheless, the role of TMEM220-AS1 in hepatocellular carcinoma (HCC) remains unclear.MethodsWe used the TCGA database to analyze differentially expressed lncRNAs. qRT-PCR was used to verify the results in a large population. Afterwards, in vitro effects of TMEM220-AS1 on HCC cells were determined by CCK-8, EdU, Flow cytometry experiment and transwell assays in HCC cells. We adopted qRT-PCR, western blot to identify epithelial-mesenchymal transition (EMT). Moreover, we adopted bioinformatics analysis, western blot, dual luciferase reporter gene assay and RIP to investigate underlying molecular mechanisms of TMEM220-AS1 function. Finally, the function of TMEM220-AS1 was verified in vivo.ResultsTMEM220-AS1 was remarkably decreasedin HCC. It was demonstrated that malignant phenotypes and EMT of HCC cells were promoted by knocking TMEM220-AS1 down both in vivo and in vitro. TMEM220-AS1, which was detected distributing mainly in the cytoplasm, worked as a miRNA sponge to sponge miR-484 and promote the level of MAGI1, therefore curbed malignant phenotypes of HCC cells.ConclusionsIn conclusion, downregulation of TMEM220-AS1promotes HCC through miR-484/MAGI1 axis.

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Circular RNA hsa_circ_0061395 accelerates hepatocellular carcinoma progression via regulation of the miR-877-5p/PIK3R3 axis

Cancer Cell International ◽

10.1186/s12935-020-01695-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yanhui Yu ◽

Lijuan Bian ◽

Renfei Liu ◽

Yitong Wang ◽

Xia Xiao

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Cycle ◽

Cell Cycle Progression ◽

Circular Rna ◽

Cell Counting ◽

Regulatory Subunit ◽

Luciferase Reporter ◽

Hcc Cells

Abstract Background Circular RNA hsa_circ_0061395 (circ_0061395) has been reported to accelerate the advancement of hepatocellular carcinoma (HCC). However, the regulatory mechanism by which circ_0061395 modulates the progression of HCC is unclear. Methods The morphology and size of exosomes were analyzed by transmission electron microscope (TEM) and nanoparticle-tracking analysis (NTA). Protein levels were detected by western blotting. Expression levels of circ_0061395, microRNA (miR)-877-5p, and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) mRNA were assessed by quantitative real time polymerase chain reaction (qRT-PCR). The proliferation, invasion, migration, cell cycle progression, and apoptosis were analyzed by cell counting kit-8 (CCK-8), plate clone, transwell, or flow cytometry assays. The targeting relationship between circ_0061395 or PIK3R3 and miR-877-5p was verified using the dual-luciferase reporter and/or RNA immunoprecipitation (RIP) assays. Xenograft assay was performed to confirm the biological function of circ_0061395 in HCC. Results Circ_0061395 was upregulated in HCC tissues, serum, cells, and serum-derived exosomes. Circ_0061395 silencing decreased tumor growth in vivo, and induced cell cycle arrest, apoptosis, repressed proliferation, invasion, and migration of HCC cells in vitro. MiR-877-5p was downregulated while PIK3R3 was upregulated in HCC. Circ_0061395 regulated PIK3R3 expression via competitively binding to miR-877-5p. MiR-877-5p inhibitor overturned circ_0061395 knockdown-mediated influence on malignant behaviors of HCC cells. PIK3R3 overexpression reversed the suppressive influence of miR-877-5p mimic on malignant behaviors of HCC cells. Conclusion Circ_0061395 facilitated HCC progression via regulating the miR-877-5p/PIK3R3 axis, providing a new perspective on the advancement of HCC.

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A Novel lncRNA loc339803 acts as CeRNA of miR-30a-5p to promote the migration and invasion of hepatocellular carcinoma cells

10.21203/rs.3.rs-56090/v1 ◽

2020 ◽

Author(s):

cailin xue ◽

xudong zhang ◽

peng gao ◽

weiwei yu ◽

xiaohan cui ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Lines ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Advanced Tumor Stage ◽

Qrt Pcr ◽

Advanced Tumor ◽

Hcc Cells

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and has an unfavorable clinical outcome. Emerging evidences have demonstrated that long noncoding RNAs (lncRNAs) play an important role in the carcinogenesis and progression of HCC. However, the clinical significances, the biological roles of most lncRNAs in HCC remain poorly understood. Methods The expression levels of lncRNA loc339803 in HCC tissues and cell lines were determined by quantitative real-time polymerase chain reaction(qRT-PCR) assay. The cellular sublocalization of loc339803 were determined by fluorescence in situ hybridization and nuclear & cytoplasmic RNA isolation assay. Western blot, CCK-8, Edu, colony formation, migration and invasion assays were used to investigate the roles of loc339803 in progression of HCC in vitro. A mouse model for lung metastasis was constructed to evaluate the role of loc339803 in HCC development in vivo. The correlations among loc339803, miR-30a-5p and SNAIL1 were validated by qRT-PCR and a dual- luciferase reporter assay. Results The expression of loc339803 was upregulated in HCC tissues and cell lines, and positively correlated with tumor size, advanced tumor stage, higher serum AFP level and poor prognosis of HCC patients. loc339803 can promote the migration and invasion of HCC cells in vivo and in vitro. Further studies demonstrated the loc339803 functioned as a competing endogenous RNA (ceRNA) by directly binding to miR-30a-5p, thus up-regulating the expression of snai1, a target gene of miR-30a-5p. Moreover, miR-30a-5p upregulation blocked the enhancement of migration and invasion of HCC cells induced by loc339803 overexpression. Conclusions Loc339803 may be oncogenic in HCC and associated with poor clinical outcomes. LncRNA loc339803 might promote the invasion and migration of HCC cells through regulating miR-30a-5p/ SNAIL1 axis.

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KLF7/VPS35 axis contributes to hepatocellular carcinoma progression through CCDC85C-activated β-catenin pathway

Cell & Bioscience ◽

10.1186/s13578-021-00585-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yarong Guo ◽

Bao Chai ◽

Junmei Jia ◽

Mudan Yang ◽

Yanjun Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Tumor Growth ◽

Luciferase Reporter ◽

Aberrant Expression ◽

Proliferation And Invasion ◽

Hcc Cells

Abstract Objective Dysregulation of KLF7 participates in the development of various cancers, but it is unclear whether there is a link between HCC and aberrant expression of KLF7. The aim of this study was to investigate the role of KLF7 in proliferation and migration of hepatocellular carcinoma (HCC) cells. Methods CCK8, colony growth, transwell, cell cycle analysis and apoptosis detection were performed to explore the effect of KLF7, VPS35 and Ccdc85c on cell function in vitro. Xenografted tumor growth was used to assess in vivo role of KLF7. Chip-qPCR and luciferase reporter assays were applied to check whether KLF7 regulated VPS35 at transcriptional manner. Co-IP assay was performed to detect the interaction between VPS35 and Ccdc85c. Immunohistochemical staining and qRT-PCR analysis were performed in human HCC sampels to study the clinical significance of KLF7, VPS35 and β-catenin. Results Firstly, KLF7 was highly expressed in human HCC samples and correlated with patients’ differentiation and metastasis status. KLF7 overexpression contributed to cell proliferation and invasion of HCC cells in vitro and in vivo. KLF7 transcriptional activation of VPS35 was necessary for HCC tumor growth and metastasis. Further, co-IP studies revealed that VPS35 could interact with Ccdc85c in HCC cells. Rescue assay confirmed that overexpression of VPS35 and knockdown of Ccdc85c abolished the VPS35-medicated promotion effect on cell proliferation and invasion. Finally, KLF7/VPS35 axis regulated Ccdc85c, which involved in activation of β-catenin signaling pathway, confirmed using β-catenin inhibitor, GK974. Functional studies suggested that downregulation of Ccdc85c partly reversed the capacity of cell proliferation and invasion in HCC cells, which was regulated by VPS35 upregulation. Lastly, there was a positive correlation among KLF7, VPS35 and active-β-catenin in human HCC patients. Conclusion We demonstrated that KLF7/VPS35 axis promoted HCC cell progression by activating Ccdc85c-medicated β-catenin pathway. Targeting this signal axis might be a potential treatment strategy for HCC.

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

Cancer Cell International ◽

10.1186/s12935-019-1093-6 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 9

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.

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LncRNA-URHC Functions as a ceRNA to Regulate Danjb9 Expression by Competitively Binding to miR-5007-3p in Hepatocellular Carcinoma

10.21203/rs.3.rs-335058/v1 ◽

2021 ◽

Author(s):

kunwei niu ◽

Shibin Qu ◽

Xuan Zhang ◽

Jimin Dai ◽

Jianlin Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Biological Effects ◽

Luciferase Reporter ◽

Underlying Mechanisms ◽

Proliferation In Vitro ◽

Hcc Cells

Abstract Background: Hepatocellular carcinoma (HCC) is often diagnosed at a late stage, when the prognosis is poor. The regulation of long non-coding RNAs (lncRNAs) plays a crucial role in HCC. However, the precise regulatory mechanisms of lncRNA signaling in HCC remain largely unknown. We study aim to investigate the underlying mechanisms of lncRNA (upregulated in hepatocellular carcinoma) URHC in HCC. Methods: RT-qPCR, fluorescence in situ hybridization (FISH) staining, EdU, colony formation, and tumor xenografts experiments were used to identify localized and biological effects of URHC on HCC cells in vitro and in vivo. The bioinformatics analysis, Dual-luciferase reporter assay, and rescue experiments revealed the potential mechanism of URHC.Results: URHC silencing may inhibit the HCC cells proliferation in vitro and in vivo. We found that URHC was mainly localized in the cytoplasm. The expression of miR-5007-3p was negatively regulated by URHC. And miR-5007-3p could reverse the effect of URHC in HCC cells. The expression of DNAJB9 was negatively regulated by miR-5007-3p but positively regulated by URHC. These suggesting of lncRNA-URHC positively regulated the level of DNAJB9 by sponging miR-5007-3p.Conclusion: Together, our study elucidated the role of URHC as a miRNA sponge in HCC, and shed new light on lncRNA-directed diagnostics and therapeutics in HCC.

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LncRNA ZFPM2-AS1 Promotes Metastasis and Epithelial-mesenchymal Transition of Hepatocellular Carcinoma via Targeting miR-3612/ADAM15 Axis

10.21203/rs.3.rs-42530/v1 ◽

2020 ◽

Author(s):

Nan Yang ◽

Tianxiang Chen ◽

Bowen Yao ◽

Liang Wang ◽

Runkun Liu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Biological Effects ◽

Luciferase Reporter Assay ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Reporter Assay ◽

Mesenchymal Transition ◽

Hcc Cells

Abstract Background: Long non-coding RNAs (lncRNAs) have obtained growing attention due to their potential effects as novel regulators in various tumors. This study aimed to investigate the expression and roles of lncRNA ZFPM2-AS1 in the progression of hepatocellular carcinoma (HCC). Methods: Transwell was used to determine migration and invasion of HCC cells in vitro. The lung metastasis mouse model was established to detect tumor metastasis of HCC in vivo. The direct binding of miR-3612 to 3'UTR of DAM15 was confirmed by luciferase reporter assay. The expression of ZFPM2-AS1 and miR-3612 in HCC specimens and cell lines were detected by real-time PCR. The correlation among ZFPM2-AS1 and miR-3612 were disclosed by a dual-luciferase reporter assay, RIP assay and biotin pull-down assay.Results: In present study, we found that ZFPM2-AS1 was up-regulated in HCC tissues and cells and its upregulation was associated with TNM stage, vascular invasion, and poor prognosis of HCC patients. Functionally, gain- and loss-of-function experiments indicated that ZFPM2-AS1 promoted cell migration, invasion and EMT progress in vitro and in vivo. ZFPM2-AS1 could function as a competing endogenous RNA (ceRNA) by sponging miR-3612 in HCC cells. Mechanically, miR-3612 inhibited HCC metastasis and alternation of miR-3612 reversed the promotive effects of ZFPM2-AS1 on HCC cells. In addition, we confirmed that ADAM15 was a direct target of miR-3612 in HCC and mediated the biological effects of miR-3612 and ZFPM2-AS1 in HCC. Curcumin, an active derivative from turmeric, exerts its anticancer effects through ZFPM2-AS1/miR-3612/ADAM15 pathway. Our data identified ZFPM2-AS1 as a novel oncogenic lncRNA and correlated malignant clinical outcomes in HCC patients. Conclusions: ZFPM2-AS1 performed as oncogenic role via targeting miR-3612 and subsequently promoted ADAM15 expression in HCC. Our results revealed that ZFPM2-AS1 could be a potential prognostic biomarker and therapeutic target for HCC.

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

10.21203/rs.3.rs-130867/v1 ◽

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.

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MicroRNA-183-5p contributes to malignant progression through targeting PDCD4 in human hepatocellular carcinoma

Bioscience Reports ◽

10.1042/bsr20201761 ◽

2020 ◽

Vol 40 (10) ◽

Author(s):

Xiaohui Duan ◽

Wei Li ◽

Peng Hu ◽

Bo Jiang ◽

Jianhui Yang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Tumor Growth ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Clinical Samples ◽

Hcc Cells

Abstract Hepatocellular carcinoma (HCC) remains one of the most common malignant tumors worldwide. The present study aimed to investigate the biological role of microRNA-183-5p (miR-183-5p), a novel tumor-related microRNA (miRNA), in HCC and illuminate the possible molecular mechanisms. The expression patterns of miR-183-5p in clinical samples were characterized using qPCR analysis. Kaplan–Meier survival curve was applied to evaluate the correlation between miR-183-5p expression and overall survival of HCC patients. Effects of miR-183-5p knockdown on HCC cell proliferation, apoptosis, migration and invasion capabilities were determined via Cell Counting Kit-8 (CCK8) assays, flow cytometry, scratch wound healing assays and Transwell invasion assays, respectively. Mouse neoplasm transplantation models were established to assess the effects of miR-183-5p knockdown on tumor growth in vivo. Bioinformatics analysis, dual-luciferase reporter assays and rescue assays were performed for mechanistic researches. Results showed that miR-183-5p was highly expressed in tumorous tissues compared with adjacent normal tissues. Elevated miR-183-5p expression correlated with shorter overall survival of HCC patients. Moreover, miR-183-5p knockdown significantly suppressed proliferation, survival, migration and invasion of HCC cells compared with negative control treatment. Consistently, miR-183-5p knockdown restrained tumor growth in vivo. Furthermore, programmed cell death factor 4 (PDCD4) was identified as a direct target of miR-183-5p. Additionally, PDCD4 down-regulation was observed to abrogate the inhibitory effects of miR-183-5p knockdown on malignant phenotypes of HCC cells. Collectively, our data suggest that miR-183-5p may exert an oncogenic role in HCC through directly targeting PDCD4. The current study may offer some new insights into understanding the role of miR-183-5p in HCC.

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