title: MicroRNA-338-3p inhibits cell proliferation in hepatocellular carcinoma by target forkhead box P4 (FOXP4).
abstract: MicroRNAs (miRNAs) are a class of small, non-coding RNAs, which have demonstrated to important gene regulators, and have critical roles in diverse biological processes including cancer cell proliferation. Previous studies suggested microRNA-338-3p (miR-338-3p) was down-regulated and play tumor suppressor roles in gastric cancer, colorectal carcinoma and lung cancer. However, the role of miR-338-3p in hepatocellular carcinoma (HCC) is still unclear. In this study, we analyzed the expression of miR-338-3p in HCC tissues and HCC cell lines. We find that miR-338-3p was downregulated in HCC tissues and cell lines. Then functional studies demonstrate ectopic miR-338-3p expression significantly suppressed the in vitro proliferation and colony formation of HCC cells and cause to cell cycle arrest. Using bio-informatic method and report assay we identified a novel miR-338-3p target, FOXP4 in HCC cells. Furthermore, knockdown of FOXP4 have the similar effects in HCC corrected with miR-338-3p. These findings suggest that miR-338-3p regulates survival of HCC cells partially through the downregulation of FOXP4. Therefore, targeting with the miR-338-3p/FOXP4 axis might serve as a novel therapeutic application to treat HCC patients.
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University Jinan 250013, Shandong, China ; Department of Oncology, Anhui Medical University Affiliated Anhui Provincial Hospital Hefei 230000, Anhui, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University Jinan 250013, Shandong, China ; Department of Oncology, Anhui Medical University Affiliated Anhui Provincial Hospital Hefei 230000, Anhui, China.
authors.forename: Yubei
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Oncology, Anhui Medical University Affiliated Anhui Provincial Hospital Hefei 230000, Anhui, China.
authors.forename: Yifu
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Oncology, Anhui Medical University Affiliated Anhui Provincial Hospital Hefei 230000, Anhui, China.
authors.forename: Chushu
authors.initials: C
authors.lastname: Ji
authors.affiliation: Department of Oncology, Anhui Medical University Affiliated Anhui Provincial Hospital Hefei 230000, Anhui, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Oncology, Jinan Central Hospital, Shandong University Jinan 250013, Shandong, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C576732:FOXP4 protein, human; D051858:Forkhead Transcription Factors; C532050:MIRN338 microRNA, human; D035683:MicroRNAs
keywords: FOXP4; HCC; cell cycle; cell growth; miR-338-3p