Dysregulated miRNA in progression of hepatocellular carcinoma: A systematic review

Mizuguchi, Yoshiaki; Tajima, Toshihiro; Yoshida, Hiroshi; Uchida, Eiji

doi:10.1111/hepr.12606

Cited by 93 publications

(68 citation statements)

References 191 publications

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“…More than 110,000 people die from liver cancer each year, accounting for 45% of all HCC deaths worldwide [2–4]. Despite therapeutic advances, the five-year survival rate of HCC is still below 5% [5–8]. HCC is the result of a multistep process which involves the accumulation of several structural and genomic alterations, gene expression profile and intracellular signal pathway alterations [9, 10].…”

Section: Introductionmentioning

confidence: 99%

The long non-coding RNA TP73-AS1 modulates HCC cell proliferation through miR-200a-dependent HMGB1/RAGE regulation

Huang

et al. 2017

J Exp Clin Cancer Res

127

115

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BackgroundP73 antisense RNA 1 T (non-protein coding), also known as TP73-AS1, is a long non-coding RNA (lncRNA) which is involved in cell proliferation and the development of tumors. However, the exact effects and molecular mechanisms of TP73-AS1 in hepatocellular carcinoma (HCC) progression are still unknown. The present study is aimed to investigate the detailed functions and the mechanism of TP73-AS1 in regulation of HCC cell proliferation.MethodsTP73-AS1 expression in HCC tissues and cell lines was determined using real-time PCR assays; the correlation of TP73-AS1 expression with clinicopathological features of HCC was analyzed. The functions of TP73-AS1 in regulation of HCC cell proliferation was evaluated using MTT and BrdU assays. The candidate upstream miRNAs of HMGB1 were screened using miRcode, miRWalk, miRanda and Target scan, verified using real-time PCR assays. The interaction between TP73-AS1 and miR-200a was confirmed using Luciferase report gene assays. The proten levels of HMGB1 signaling-related factors in response to co-processing TP73-AS1 knockdown and miR-200a inhibition were determined using Western blot assays and ELISA. Further, miR-200a, HMGB1 mRNA and RAGE mRNA and their correlations in HCC tissues were determined.ResultsTP73-AS1 was upregulated in HCC tissues and cell lines. High TP73-AS1 expression was correlated with worse clinicopathological features, poorer prognosis and shorter survival. Knockdown of TP73-AS1 inhibited the HCC proliferation and the expression levels of HMGB1, RAGE and NF-κB in HCC cells. By using online tools, we screened out several candidate upstream miRNAs of HMGB1, among which miR-200a overexpression inhibited HMGB1 mRNA expression the most significantly. By using luciferase assays, we confirmed that miR-200a could directly bind to TP73-AS1 and the 3’UTR of HMGB1; TP73-AS1 competed with HMGB1 for miR-200a binding. MiR-200a inhibition could up-regulate HMGB1, RAGE, NF-κB expression as well as NF-κB regulated cytokines levels, which could be partially restored by si-TP73-AS1. In HCC tissues, miR-200a was down-regulated while HMGB1 and RAGE were up-regulated; TP73-AS1 was inversely correlated with miR-200a, while positively correlated with HMGB1 and RAGE, respectively.ConclusionOur data indicated that TP73-AS1 might be an oncogenic lncRNA that promoted proliferation of HCC and could be regarded as a therapeutic target in human HCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0519-z) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

The long non-coding RNA TP73-AS1 modulates HCC cell proliferation through miR-200a-dependent HMGB1/RAGE regulation

Huang

et al. 2017

J Exp Clin Cancer Res

127

115

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“…The discovery of microRNAs (miRNAs) provides a new understanding of tumor development and progression in HCC [5]. The negative regulation of miRNA on mRNAs can serve as oncomirs or tumor suppressors and has constantly been found in diverse forms of cancer.…”

Section: Introductionmentioning

confidence: 99%

MiR-490-5p Suppresses Cell Proliferation and Invasion by Targeting BUB1 in Hepatocellular Carcinoma Cells

Liu

et al. 2017

Pharmacology

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Objective: To verify that miR-490-5p could influence hepatocellular carcinoma (HCC) cells' proliferation, invasion, cycle, and apoptosis by targeting BUB1. Methods: Quantitative real time-PCR (QRT-PCR) was used to determine the miR-490-5p expression. Immunohistochemistry, qRT-PCR, and Western blot were employed to detect BUB1 and transforming growth factor-beta (TGFβ/Smad) signaling-related proteins expression in hepatic tissues and cells. The luciferase assay was used to confirm the targeting relationship between miR-490-5p and BUB1. The Cell Counting Kit-8, colony formation, Transwell invasion, scratch healing assays, and flow cytometry analysis were conducted to evaluate HCC cells proliferation, invasion, migration, and apoptosis alteration after transfection. Results: In HCC tissues and cells, lower expression of miR-490-5p was detected, while BUB1 was overexpressed than controls. The upregulation of miR-490-5p inhibited BUB1 expression and the overexpression of miR-490-5p or the under-expression of BUB1 inhibited HCC cells proliferation, migration, invasion, and increased the apoptosis rate. Conclusion: MiR-490-5p could regulate TGFβ/Smad signaling pathways by inhibiting BUB1, which could then inhibit HCC cells proliferation, invasion, and migration as well as decrease cell viability and increase apoptosis.

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“…T24 cells (3x10 5 ) were seeded into 24-well plates and transfected with miR-96 and/or plasmid HERG1 using Lipofectamine 2000 according to the manufacturer's protocol, as aforementioned. Plasmids (cat.…”

Section: Reverse Transcription-polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

“…miRNAs function primarily through the targeted degradation of mRNAs and inhibition of translation into proteins. Therefore, miRNAs have numerous biological activities (5,6). Notably, miRNAs perform critical functions in the occurrence and development of lung, liver, gastric, cervical, breast, and colon cancer (7,8).…”

Section: Introductionmentioning

confidence: 99%

Anticancer effect of miR-96 inhibitor in bladder cancer cell lines

et al. 2018

Oncol Lett

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Abstract. The present study aimed to investigate the role of microRNA-96 (miR-96) in the proliferation, invasion and apoptosis of bladder cancer cell lines, and the associated mechanisms. The expression of miR-96 and human ether-à-go-go-related (HERG1) potassium channel in the normal uroepithelium SV-HUC-1 cell line, and bladder cancer T24 and 5637 cell lines were examined using reverse transcription-polymerase chain reaction or/and western blotting. Transfection with miR-96 inhibitor or scrambled control (SC) was used to study the biological activities of miR-96 in bladder cancer cell lines. MTT, flow cytometric and Transwell assays were applied to detect cell viability, apoptosis and invasion, respectively. A dual-luciferase reporter assay was applied to determine the association between miR-96 and HERG1 expression. As demonstrated, miR-96 was highly expressed in the two bladder cancer cell lines, particularly in T24 cells. Following transfection with miR-96 inhibitor, miR-96 expression was significantly reduced in the T24 cell line, compared with SC. The miR-96 inhibitor suppressed cell proliferation and invasion, promoted apoptosis and arrested the cell cycle at the G 1 phase. Consistently, HERG1 was also highly expressed in the two bladder cancer cell lines at the mRNA and protein level, but not in the normal uroepithelium cell line. The miR-96 inhibitor also significantly decreased HERG1 expression compared with SC. The results of the dual-luciferase reporter assay indicated that miR-96 directly targeted wild-type HERG1. In conclusion, miR-96 inhibitor exhibited anticancer effects on bladder cancer cells by inhibiting proliferation and invasion of cells, and promoting their apoptosis. HERG1 was an important target of miR-96. These results provided experimental evidence supporting miR-96 as a therapeutic target for patients with bladder cancer.

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Dysregulated miRNA in progression of hepatocellular carcinoma: A systematic review

Cited by 93 publications

References 191 publications

The long non-coding RNA TP73-AS1 modulates HCC cell proliferation through miR-200a-dependent HMGB1/RAGE regulation

The long non-coding RNA TP73-AS1 modulates HCC cell proliferation through miR-200a-dependent HMGB1/RAGE regulation

MiR-490-5p Suppresses Cell Proliferation and Invasion by Targeting BUB1 in Hepatocellular Carcinoma Cells

Anticancer effect of miR-96 inhibitor in bladder cancer cell lines

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