Abstract
BackgroundLiver cancer is among the most common malignancy worldwide. Hepatocellular carcinoma (HCC), the principal histological subtype of liver cancer, is globally the third most common cause of cancer-related mortality. The high rates of recurrence and metastasis contribute to the poor prognosis of HCC patients. In recent years, increasing evidence has shown that microRNAs (miRNAs) are involved in the tumorigenesis, progression, and prognosis of HCC.MethodsTo screen for key candidate miRNAs in HCC, three microarray datasets were downloaded from Gene Expression Omnibus (GEO). The sole common differentially expressed miRNA (DEmiR) observed in the above three datasets using a Venn diagram was microRNA-211-5p (miR-211-5p). The expression of miR-211-5p from HCC tissues was measured in several HCC cell lines. Additionally, using Kaplan–Meier plots, the potential prognostic value of miR-211-5p in HCC was analyzed. Cell counting kit-8 (CCK-8) and transwell assays examined the ability of miR-211-5p to induce cell proliferation, migration, and invasion in HCC cultures. The interaction of miR-211-5p and Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4) was assessed both theoretically and using a luciferase reporter assay. Finally, the ability of miR-211-5p to modulate tumorigenesis in HCC in vivo was assessed after establishing a xenograft model.ResultsqRT-PCR demonstrated that the relative expression of miR-211-5p was considerably down-regulated in HCC tissues and cell lines compared with normal tissue. Kaplan–Meier plots indicated that HCC patients with decreased expression of miR-211-5p had poor overall survival. Upregulation of miR-211-5p in vitro consistently suppressed cell proliferation, migration, and invasion. In contrast, enhanced expression of ACSL4 promoted a malignant phenotype in HCC cells. Importantly, we discovered that ACSL4 was a direct downstream target of miR-211-5p in HCC, and that miR-211-5p suppressed the malignant phenotype by inhibition of ACSL4 expression. Furthermore, miR-211-5p overexpression impaired tumorigenesis and growth of HCC in vivo.ConclusionsTargeting miR-211-5p and the downstream gene ACSL4 will possibly provide novel insight and represents a promising approach to future therapy of HCC patients.
Highlights
IntroductionHepatocellular carcinoma (HCC), the principal histological subtype of liver cancer, is globally the third most common cause of cancer-related mortality
Liver cancer is among the most common malignancy worldwide
MiR-211-5p expression in liver cancer samples was not significantly different from adjacent normal samples based on the Cancer Genome Atlas (TCGA) cohorts, it was considerably down-regulated in 30 pairs of Hepatocellular carcinoma (HCC) tissues compared with matched adjacent tumor-free tissues from patients in clinic or real-world cohorts (Fig. 1b, c)
Summary
Hepatocellular carcinoma (HCC), the principal histological subtype of liver cancer, is globally the third most common cause of cancer-related mortality. In recent years, increasing evidence has shown that microRNAs (miRNAs) are involved in the tumorigenesis, progression, and prognosis of HCC. Primary liver cancer has become the seventh most common cancer and the second most common cause of cancer mortality worldwide, responsible for 819 000 deaths per year [1]. According to data from the National Central Cancer Registry of China in 2015, primary liver cancer has become among the most malignant tumors causing. Hepatocellular carcinoma (HCC) accounts for up to 90% of all primary hepatic malignancies, with poor prognosis in regions with high prevalence of hepatitis B and C [3]. Identification of abnormally-expressed miRNAs and their downstream target genes in HCC enhance our understanding of the potential pathogenesis of HCC and represents a promising strategy for the diagnosis, treatment, and prognosis of HCC
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