MicroRNA-4516 suppresses pancreatic cancer development via negatively regulating orthodenticle homeobox 1.

Abstract

Pancreatic cancer remains one of the most lethal human cancers without efficient therapeutic strategy. MicoRNAs (miRNAs) are a group of small non-coding RNAs involved in multiple biological processes including tumor development and progression. In this study, we investigated the expression and function of miR-4516 in pancreatic cancer. MiR-4516 was low-expressed in pancreatic cancer tissues and cell lines. Overexpression of miR-4516 inhibited pancreatic cancer cell proliferation, migration and invasion, while promoted cell apoptosis in vitro. Further, overexpression of miR-4516 suppressed xenograft pancreatic tumor growth in vivo. Bioinformatics analysis was performed and miR-4516 was predicted to negatively regulate orthodenticle homeobox 1 (OTX1) expression by binding to its 3'-UTR. Consistently, OTX1 was highly expressed in pancreatic cancer tissues and cell lines. Knockdown of OTX1 expression suppressed pancreatic cancer cell migration and invasion, with down-regulated MMP2 and MMP9 expression. Moreover, we demonstrated that miR-4516 regulated pancreatic cancer cell growth, migration, invasion and apoptosis via targeting OTX1. Overexpression of OTX1 could partially abrogate the inhibitory effect of miR-4516. Taken together, we conclude that miR-4516 could function as a tumor suppressor via targeting OTX1. These findings suggest that miR-4516/OTX1 axis might be a novel therapeutic target for miRNA-based therapy for pancreatic cancer patients.

• Authors: Shuo Chen, Meng Xu, Jing Zhao, Jiaqi Shen, Junhui Li, Yang Liu, Gang Cao, Jiancang Ma, Weizhou He, Xi Chen, Tao Shan
• Journal: International journal of biological sciences (Int J Biol Sci) Vol. 16 Issue 12 Pg. 2159-2169 ( 2020) ISSN: 1449-2288 [Electronic] Australia
• PMID: 32549762 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The author(s).

Chemical References

• MIRN-4516 microRNA, human
• MicroRNAs
• OTX1 protein, human
• Otx Transcription Factors

Topics

• Animals
• Cell Line, Tumor
• Down-Regulation
• Gene Expression Regulation, Neoplastic
• Humans
• Mice
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Neoplasms, Experimental
• Otx Transcription Factors (genetics, metabolism)
• Pancreatic Neoplasms (metabolism)