title: Role of miR-181a-5p and endoplasmic reticulum stress in the regulation of myogenic differentiation.
abstract: Accumulating evidence has indicated that microRNAs (miRNAs) and endoplasmic reticulum (ER) stress play critical roles in myoblast differentiation. However, the regulation roles of miRNAs and ER stress in myogenic differentiation have not been fully revealed and need to be further studied. Here, we discovered that the expression levels of miR-181a-5p were strongly upregulated during C2C12 cell differentiation. miR-181a-5p overexpression promoted ER stress and differentiation of C2C12 cells, which was accompanied by increasing expression levels of marker genes related to ER stress-mediated apoptosis and myogenic differentiation. Opposite results were observed after inhibition of the miR-181a-5p expression. The gain- and loss-of-function experiments on C2C12 cells showed that miR-181a-5p affected the development of muscle fiber type, but had no significant influence on C2C12 cell proliferation. In the ER-stressed C2C12 cells induced by thapsigargin (Tg), the expression levels of both miR-181a-5p and marker genes related to ER stress and myogenesis were upregulated. In the ER-stressed C2C12 cells and porcine muscle fibroblast (PMF) cells pretreated with Tg, we found that miR-181a-5p targeted glucose-regulated protein, 78kDa/binding immunoglobulin protein (GRP78/BIP), and influenced cell apoptosis. In conclusion, these results indicate that miR-181a-5p and ER stress have positive synergistic effects on myogenic differentiation by increasing the expression levels of myogenic differentiation key genes and activating the ER stress-mediated apoptosis signaling pathway.
authors.affiliation: Department of Zoology, College of Life Science, Sichuan Agricultural University, Ya'an, Sichuan 625014, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Zoology, College of Life Science, Sichuan Agricultural University, Ya'an, Sichuan 625014, China.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Tao
authors.affiliation: Department of Zoology, College of Life Science, Sichuan Agricultural University, Ya'an, Sichuan 625014, China.
authors.forename: Huaming
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Zoology, College of Life Science, Sichuan Agricultural University, Ya'an, Sichuan 625014, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Tang
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Li
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.
authors.forename: Anan
authors.initials: A
authors.lastname: Jiang
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.
authors.forename: Surong
authors.initials: S
authors.lastname: Shuai
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.
authors.forename: Jideng
authors.initials: J
authors.lastname: Ma
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.
authors.forename: Long
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Zoology, College of Life Science, Sichuan Agricultural University, Ya'an, Sichuan 625014, China.
authors.forename: Anxiang
authors.initials: A
authors.lastname: Wen
authors.affiliation: Department of Zoology, College of Life Science, Sichuan Agricultural University, Ya'an, Sichuan 625014, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Zoology, College of Life Science, Sichuan Agricultural University, Ya'an, Sichuan 625014, China.
authors.forename: Guangxiang
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Zoology, College of Life Science, Sichuan Agricultural University, Ya'an, Sichuan 625014, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xie
authors.affiliation: Department of Zoology, College of Life Science, Sichuan Agricultural University, Ya'an, Sichuan 625014, China.
authors.forename: Jiayun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Zoology, College of Life Science, Sichuan Agricultural University, Ya'an, Sichuan 625014, China.
authors.forename: Tao
authors.initials: T
authors.lastname: He
authors.affiliation: Department of Zoology, College of Life Science, Sichuan Agricultural University, Ya'an, Sichuan 625014, China. Electronic address: jiangyz04@163.com.
authors.forename: Yanzhi
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130, China. Electronic address: xuewei.li@sicau.edu.cn.
authors.forename: Xuewei
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D018507:Gene Expression Regulation, Developmental; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D013552:Swine
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D035683:MicroRNAs; C529100:mirn181 microRNA, mouse
keywords: Apoptosis; Endoplasmic reticulum stress; Myogenic differentiation; miR-181a-5p