Int J Biol Sci 2020; 16(14):2612-2627. doi:10.7150/ijbs.46822

Research Paper

MiR-216a-5p inhibits tumorigenesis in Pancreatic Cancer by targeting TPT1/mTORC1 and is mediated by LINC01133

Jian Zhang1*, Shuohui Gao3*, Yandong Zhang1*, Huixin Yi2, Mengxian Xu2, Jialun Xu5, HuanLiu1, Zhichen Ding1, Hongbin He6, Hongmei Wang6, Zhuo Hao2, Liankun Sun4, Yan Liu2✉, Feng Wei1✉

1. Department of Hepatobiliary and Pancreas Surgery, Jilin University First Hospital, Changchun, China.
2. Genetic Engineering Laboratory of PLA, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, China.
3. Department of Gastrointestinal Colorectal Surgery, China-Japan Union hospital of Jilin University, Changchun, China.
4. Department of Pathophysiology, College of Basic Medicine Sciences, Jilin University, Changchun, China.
5. Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University.
6. Ruminant Diseases Research Center, College of Life Sciences, Shandong Normal University, Jinan, China.
*These authors contributed equally to this work.

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Citation:
Zhang J, Gao S, Zhang Y, Yi H, Xu M, Xu J, HuanLiu , Ding Z, He H, Wang H, Hao Z, Sun L, Liu Y, Wei F. MiR-216a-5p inhibits tumorigenesis in Pancreatic Cancer by targeting TPT1/mTORC1 and is mediated by LINC01133. Int J Biol Sci 2020; 16(14):2612-2627. doi:10.7150/ijbs.46822. Available from http://www.ijbs.com/v16p2612.htm

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Abstract

MiR-216a-5p has opposite effects on tumorigenesis and progression in the context of different tumors, acting as either a tumor suppressor or an oncogene. However, the expression and function of miR-216a-5p in pancreatic cancer (PC) is not well characterized.

In this study, we found miR-216a-5p was significantly downregulated in PC tissues and cell lines, which showed a negative correlation with peripancreatic lymph, perineural invasion and TNM stage of PCs patients. We made use of functional assays to reveal that miR-216a-5p inhibited growth and migration of PC cells in vitro and in vivo. Then, by employing the bioinformatics analysis and luciferase reporter assay, we demonstrated TPT1 was a potential target of miR-216a-5p, which contributes to tumor malignance by mediating mTORC1 pathway-associated autophagy. Furthermore, bioinformatics analysis and RNA pulldown confirmed that miR-216a-5p was mediated by LINC01133, which sponge miR-216a-5p, as a competing endogenous RNA (ceRNA). Collectively, our study revealed an important role of LINC01133/miR-216a-5p/TPT1 axis in the genesis and progression of PCs, which provides potential biomarkers for clinical diagnosis and therapy of PCs.

Keywords: LINC01133, pancreatic cancer, miR-216a-5p, TPT1, tumor progression