miR-9-5p facilitates hepatocellular carcinoma cell proliferation, migration and invasion by targeting ESR1
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miR‑9‑5p facilitates hepatocellular carcinoma cell proliferation, migration and invasion by targeting ESR1 Libing Wang1 · Mingxin Cui1 · Daming Cheng1 · Fengzhi Qu1 · Jingkun Yu1 · Yanbin Wei2 · Ling Cheng2 · Xiaotang Wu2 · Xiaogang Liu1 Received: 13 May 2020 / Accepted: 23 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The study aimed to explore the relationship between miR-9-5p and ESR1, and clarify the underlying functional mechanism in the occurrence and development of hepatocellular carcinoma (HCC). Expression data including miRNAs and mRNAs of HCC downloaded from TCGA database were processed for differential analysis, and corresponding clinical data were collected for survival analysis to identify the target miRNA miR-9-5p. Bioinformatics databases were applied for predicting downstream target mRNAs of miR-9-5p. qRT-PCR was used to evaluate expression of miR-9-5p. Western blot was used to detect protein expression of ESR1. MTT, wound healing assay and Transwell assay were used to detect HCC cell proliferation, migration and invasion, respectively. Dual-luciferase reporter gene assay was used to identify the targeting relationship between miR-9-5p and ESR1. Research suggested that miR-9-5p was highly expressed in HCC cells but ESR1 was poorly expressed. Overexpression of miR-9-5p could improve the proliferation, invasion and migration of cells. Dual-luciferase reporter assay showed that ESR1 was the downstream target of miR-9-5p in HCC. Overexpression of miR-9-5p markedly reduced ESR1 mRNA and protein levels in HCC cells, whereas inhibition of miR-9-5p expression produced the contrary results. Silencing ESR1 could noticeably reverse the effect of miR-9-5p knockdown on the proliferation, migration and invasion of HCC cells. As an oncogene, miR-9-5p fostered the proliferation, migration and invasion of HCC cells by targeting and inhibiting ESR1 expression. Keywords miR-9-5p · ESR1 · Hepatocellular carcinoma · Proliferation · Migration · Invasion
Introduction Hepatocellular carcinoma (HCC) is the sixth most often diagnosed cancer and the fourth leading cause of cancer death around the world, with approximately 841,000 new cases and 782,000 deaths every year [1]. Due to the fact that HCC is difficult to be diagnosed in the early stage and develops in a fast rate, it is often confirmed in an advanced stage. Libing Wang and Mingxin Cui have contributed equally to this work. * Xiaogang Liu [email protected] 1
Department of Hepatobiliary Surgery, Tangshan Gongren Hospital, No. 27 Cultural Road, Lubei District, Tangshan 063000, Hebei, China
Shanghai Engineering Research Center of Pharmaceutical Translation, Shanghai 200231, China
2
Additionally, targeted drug is in deficiency to treat HCC currently, therefore the survival rate is extremely low [2, 3]. Therefore, development of novel targets for HCC treatment is an important research goal. MicroRNAs (miRNAs) exert a crucial role in physiological and pathological processes by post-transcriptional modification of
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