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miR-744-5p Inhibits Multiple Myeloma Proliferation, Epithelial Mesenchymal Transformation and Glycolysis by Targeting SOX12/Wnt/β-Catenin Signaling

Authors Guo B, Xiao C, Liu Y, Zhang N, Bai H, Yang T, Xiang Y, Nan Y, Li Q, Zhang W, Huang D

Received 3 July 2020

Accepted for publication 17 October 2020

Published 22 February 2021 Volume 2021:14 Pages 1161—1172

DOI https://doi.org/10.2147/OTT.S270636

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Takuya Aoki


Bingling Guo,1,* Chunyan Xiao,1,* Yumin Liu,2 Ning Zhang,3 Hao Bai,4 Tao Yang,1 Ying Xiang,1 Yingyu Nan,1 Qiying Li,1 Wenjun Zhang,1 Dehong Huang1

1Department of Hematology and Oncology, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China; 2Medical Records Management Division, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China; 3Intensive Care Unit, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China; 4Pharmacy Services, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Dehong Huang
Department of Hematology and Oncology, Chongqing University Cancer Hospital, No. 181 Hanyu Road, Chongqing, People’s Republic of China
Tel +86 23-65311341
Email dehong_h012436@163.com

Purpose: This study investigated the function and molecular mechanisms of miR-744-5p in multiple myeloma (MM).
Methods: miR-744-5p and SRY-related high-mobility-group box 12 (SOX12) expression in clinical tissues and MM cells was monitored by quantitative real-time polymerase chain reactions and Western blot. miR-744-5p expression in MM cells was regulated by transfection. Cell proliferation was researched by cell counting kit-8 assay and plate clone formation experiment. Transwell experiment was utilized for migration and invasion detection. Glycolysis test was conducted for the detection of glucose uptake and lactate production of MM cells. The relationship between miR-744-5p and SOX12 was determined by dual-luciferase reporter gene assay and RNA pull-down experiment. In vivo experiment was conducted using nude mice.
Results: miR-744-5p expression was reduced in MM patients (P< 0.01). Low miR-744-5p expression was associated with lower 60-month survival in MM patients (P=0.0402). miR-744-5p overexpression inhibited MM cells proliferation, invasion, migration, glucose uptake, lactate production, and epithelial mesenchymal transformation (EMT) (P< 0.01). miR-744-5p directly inhibited SOX12 expression. miR-744-5p silencing promoted MM cells proliferation, invasion, migration, glucose uptake, lactate production, and EMT by elevating SOX12 (P< 0.01). miR-744-5p inhibited the growth of MM xenograft tumors in vivo (P< 0.001).
Conclusion: miR-744-5p inhibits MM cells proliferation, invasion, migration, EMT, and glycolysis by targeting SOX12/Wnt/β-catenin.

Keywords: MM, miR-744-5p, SOX12, EMT, glycolysis

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