Identification of MiR-211-5p as a tumor suppressor by targeting ACSL4 in Hepatocellular Carcinoma
- PDF / 2,991,599 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 77 Downloads / 171 Views
Journal of Translational Medicine Open Access
RESEARCH
Identification of MiR‑211‑5p as a tumor suppressor by targeting ACSL4 in Hepatocellular Carcinoma Xia Qin2, Jian Zhang3,4, Yu Lin5, Xue‑ming Sun6, Jia‑ning Zhang7 and Zhi‑qiang Cheng1*
Abstract Background: Liver 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. Methods: To 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 Syn‑ thetase 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. Results: qRT-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 over‑ expression impaired tumorigenesis and growth of HCC in vivo. Conclusions: Targeting miR-211-5p and the downstream gene ACSL4 will possibly provide novel insight and repre‑ sents a promising approach to future therapy of HCC patients. Keywords: MicroRNA-211-5p, ACSL4, Hepatocellular carcinoma, Tumorigenesis, Migration, Invasion
*Correspondence: [email protected] † Xia Qin, Jian Zhang and Yu Lin contributed equally to this work 1 Department of General Surgery, Qilu Hospital of Shandong University, No. 107, western culture road, Jinan, China Full list of author information is available at the end of the article
Background Primary liver cancer has become the seventh most common cancer and the second most common cause of cancer mortality worldwide, r
Data Loading...
