Ectopic expression of miR-494 inhibited the proliferation, invasion and chemoresistance of pancreatic cancer by regulating SIRT1 and c-Myc.

Abstract

Recent researches demonstrate that microRNAs (miRNAs) are deregulated in numerous cancers and involved in tumorigenesis, whereas their influences on pancreatic cancer (PC) still need further elucidation. The present research revealed that miR-494 was significantly decreased in PC cell lines and tissues. Functional study showed that overexpressed miR-494 could remarkably inhibit proliferation of PC cells both in vitro and in vivo, which was due to induction of apoptosis, G1-phase arrest and senescence. Moreover, upregulated miR-494 significantly prohibited invasion of PC cells. Meanwhile, both c-Myc and SIRT1 was identified as targets of miR-494 through dual luciferase assay and further confirmed by the reverse correlation between miR-494 and c-Myc/SIRT1 in PC samples. Furthermore, co-transfection with c-Myc-RNAi and SIRT1-RNAi synergistically reduced c-Myc and SIRT1 expression, and inhibited proliferation of PC, which simulated the effects of miR-494 overexpression. On the contrary, co-overexpression of c-Myc and SIRT1 effectively rescued inhibition of overexpressed miR-494 on PC cells. The clinical characteristics further revealed that low miR-494 correlated with larger tumor size, late tumor node metastasis stage, lymphatic invasion, distant metastasis and poor prognosis. In conclusion, the present study indicated that miR-494 might serve as predictor and inhibitor in PC by directy downregulating the loop of c-Myc and SIRT1.

• Authors: Y Liu, X Li, S Zhu, J-g Zhang, M Yang, Q Qin, S-c Deng, B Wang, K Tian, L Liu, Y Niu, C-y Wang, G Zhao
• Journal: Gene therapy (Gene Ther) Vol. 22 Issue 9 Pg. 729-38 (Sep 2015) ISSN: 1476-5462 [Electronic] England
• PMID: 25965392 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN494 microRNA, human
• MYC protein, human
• MicroRNAs
• Proto-Oncogene Proteins c-myc
• SIRT1 protein, human
• Sirtuin 1

Topics

• Aged
• Animals
• Cell Line, Tumor
• Cell Proliferation
• Drug Resistance, Neoplasm
• Ectopic Gene Expression
• Female
• Heterografts
• Humans
• Male
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (metabolism)
• Middle Aged
• Neoplasm Invasiveness
• Pancreatic Neoplasms (diagnosis, metabolism)
• Prognosis
• Proto-Oncogene Proteins c-myc (metabolism)
• Sirtuin 1 (metabolism)