J Cancer 2020; 11(18):5466-5477. doi:10.7150/jca.46351

Research Paper

DGCR5 Promotes Gallbladder Cancer by Sponging MiR-3619-5p via MEK/ERK1/2 and JNK/p38 MAPK Pathways

Shilei Liu1,2*, Bingfeng Chu1,2*, Chen Cai1,2, Xiangsong Wu1,2, Wenyan Yao1, Ziyou Wu1, Ziyi Yang1,2*, Fengnan Li1,2*, Yingbin Liu1,2*, Ping Dong1,2✉, Wei Gong1,2✉

1. Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China
2. Shanghai Key Laboratory of Biliary Tract Disease Research, No. 1665 Kongjiang Road, Shanghai 200092, China
* These authors contributed equally to this work.

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Citation:
Liu S, Chu B, Cai C, Wu X, Yao W, Wu Z, Yang Z, Li F, Liu Y, Dong P, Gong W. DGCR5 Promotes Gallbladder Cancer by Sponging MiR-3619-5p via MEK/ERK1/2 and JNK/p38 MAPK Pathways. J Cancer 2020; 11(18):5466-5477. doi:10.7150/jca.46351. Available from https://www.jcancer.org/v11p5466.htm

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Abstract

Gallbladder cancer (GBC) is a highly aggressive malignant cancer with poor prognosis. Long noncoding RNA (lncRNA) DiGeorge syndrome critical region gene (DGCR5) has been reported to participate in various types of cancers, but its role in GBC remains largely unknown. This study aimed to explore the functions and mechanisms of DGCR5 in GBC. Here, we found that DGCR5 was upregulated in GBC tissues and cell lines. Through functional experiments, it was demonstrated that silence of DGCR5 significantly suppressed the cell proliferation, migration, invasion, and induced apoptosis and cell cycle arrest in GBC cells. In addition, miR-3619-5p was predicted and further verified as the target of DGCR5. Moreover, miR-3619-5p was observed downregulated in GBC tissues and cell lines, and miR-3619-5p mimics repressed the GBC cell proliferation, migration, invasion and could be rescued by DGCR5 overexpression. Mechanistically, it was found that DGCR5 knockdown and miR-3619-5p mimics inactivated the MEK/ERK1/2 and JNK/p38 MAPK pathways. In addition, rescue experiments indicated that inhibition of MEK/ERK1/2 and JNK/p38 MAPK pathways could reverse the effects of DGCR5 overexpression on cell proliferation, migration and invasion. Finally, xenograft model assay was used to validate that knockdown of DGCR5 suppressed GBC via regulating MEK/ERK1/2 and JNK/p38 MAPK pathways in vivo. Taken together, it was uncovered in our study that DGCR5 exerts an oncogenic role by sponging miR-3619-5p and activating MEK/ERK1/2 and JNK/p38 MAPK pathways in GBC progression.

Keywords: DGCR5, miR-3619-5p, gallbladder cancer, MERK/ERK1/2, JNK/p38 PAPK