J Cancer 2022; 13(6):1808-1819. doi:10.7150/jca.65071 This issue

Research Paper

Silencing LINC00491 Inhibits Pancreatic Cancer Progression through MiR-188-5p-induced Inhibition of ZFP91

Zhi Fang1,2, Bin Ruan1,2, Min Zhong1,2, Jianping Xiong1,2, Yanxia Jiang3, Zhiwang Song1,2✉

1. Department of Oncology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi province, People's Republic of China.
2. Jiangxi Key Laboratory for Individualized Cancer Therapy, Nanchang, Jiangxi province, People's Republic of China.
3. Department of Rehabilitation Medicine, the First Affiliated Hospital of Nanchang University, Jiangxi province, People's Republic of China.

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Citation:
Fang Z, Ruan B, Zhong M, Xiong J, Jiang Y, Song Z. Silencing LINC00491 Inhibits Pancreatic Cancer Progression through MiR-188-5p-induced Inhibition of ZFP91. J Cancer 2022; 13(6):1808-1819. doi:10.7150/jca.65071. Available from https://www.jcancer.org/v13p1808.htm

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Abstract

Graphic abstract

Background: Pancreatic cancer is recognized as one of the most malignant tumors with poor prognosis. Recently, long noncoding RNAs (lncRNAs) are considered as a potential prognostic biomarker of PC. However, the concrete biological effect of lncRNAs in PC remains unmasked. Herein, we explored the mechanism of LINC00491 in PC.

Methods: Quantitative real-time PCR (qRT-PCR) was administrated to detected the expression of LINC00491 in PC tissues and cell lines. Loss-of-function experiment in vitro and in vivo was carried out to figure out the biological effects of LINC00491 on PC carcinogenesis. Luciferase reporter assay, subcellular fractionation, western blotting, pull-down assay and RNA immunoprecipitation assay were further used to explore the mechanism of PC tumorigenesis of LINC00491.

Results: An increase of LINC00491 was detected in PC cell lines and tissues. Silencing LINC00491 in vitro and in vivo subsequently hindered cell migration, invasion, proliferation and tumor growth, respectively. Further research confirmed a negative and a positive connection of LINC00491 with microRNA 188-5p (miR-188-5p) level and Zinc finger protein 91 (ZFP91), a target of miR-188-5p, respectively. qRT-PCR and western blotting found that miR-188-5p was upregulated while LINC00491 was downregulated, concomitant with ZFP91 decreasing in PC cells or node mouse tumors, which could be significantly restored by inhibiting miR-188-5p. Besides, overexpression of miR-188-5p partially restored the inhibitory effect of LINC00491 diminution on proliferation, migration, and invasion of PC cells.

Conclusion: LINC00491 promotes PC proliferation, migration, invasion via the miR-188-5p/ZFP91 axis, suggesting LINC00491 could be a new therapeutic target for PC.

Keywords: pancreatic cancer, LINC00491, miR-188-5p, ZFP91, carcinogenesis