Natural Antisense RNA Foxk1-AS Promotes Myogenic Differentiation by Inhibiting Foxk1 Activity

Overview

Journal Cell Commun Signal

Publisher Biomed Central

Specialties Biochemistry
Cell Biology

Date 2022 Jun 1

PMID 35642035

Authors

Chun Li

Hao Shen

Meng Liu

Siguang Li

Yuping Luo

Affiliations

Soon will be listed here.

Abstract

Background: Natural antisense RNAs are RNA molecules that are transcribed from the opposite strand of either protein-coding or non-protein coding genes and have the ability to regulate the expression of their sense gene or several related genes. However, the roles of natural antisense RNAs in the maintenance and myogenesis of muscle stem cells remain largely unexamined.

Methods: We analysed myoblast differentiation and regeneration by overexpression and knockdown of Foxk1-AS using lentivirus and adeno-associated virus infection in C2C12 cells and damaged muscle tissues. Muscle injury was induced by BaCl and the regeneration and repair of damaged muscle tissues was assessed by haematoxylin-eosin staining and quantitative real-time PCR. The expression of myogenic differentiation-related genes was verified via quantitative real-time PCR, Western blotting and immunofluorescence staining.

Results: We identified a novel natural antisense RNA, Foxk1-AS, which is transcribed from the opposite strand of Foxk1 DNA and completely incorporated in the 3' UTR of Foxk1. Foxk1-AS targets Foxk1 and functions as a regulator of myogenesis. Overexpression of Foxk1-AS strongly inhibited the expression of Foxk1 in C2C12 cells and in tibialis anterior muscle tissue and promoted myoblast differentiation and the regeneration of muscle fibres damaged by BaCl. Furthermore, overexpression of Foxk1-AS promoted the expression of Mef2c, which is an important transcription factor in the control of muscle gene expression and is negatively regulated by Foxk1.

Conclusion: The results indicated that Foxk1-AS represses Foxk1, thereby rescuing Mef2c activity and promoting myogenic differentiation of C2C12 cells and regeneration of damaged muscle fibres. Video Abstract.

Citing Articles

Foxk1 promotes bone formation through inducing aerobic glycolysis.

Liu C, Feng N, Wang Z, Zheng K, Xie Y, Wang H Cell Death Differ. 2024; 31(12):1650-1663.

PMID: 39232134 PMC: 11618307. DOI: 10.1038/s41418-024-01371-w.

Unraveling the role of Major Vault Protein as a novel immune-related biomarker that promotes the proliferation and migration in pancreatic adenocarcinoma.

Wu X, Hao L, Lin J, Guo X, Luo Y, Li C Front Immunol. 2024; 15:1399222.

PMID: 39026679 PMC: 11254802. DOI: 10.3389/fimmu.2024.1399222.

References

Zhu M, Liu J, Xiao J, Yang L, Cai M, Shen H . Lnc-mg is a long non-coding RNA that promotes myogenesis. Nat Commun. 2017; 8:14718. PMC: 5353601. DOI: 10.1038/ncomms14718. View

Chal J, Pourquie O . Making muscle: skeletal myogenesis and . Development. 2017; 144(12):2104-2122. DOI: 10.1242/dev.151035. View

Xia H, Jing H, Li Y, Lv X . RETRACTED: Long noncoding RNA HOXD-AS1 promotes non-small cell lung cancer migration and invasion through regulating miR-133b/MMP9 axis. Biomed Pharmacother. 2018; 106:156-162. DOI: 10.1016/j.biopha.2018.06.073. View

Liu X, Fu Q, Li S, Liang N, Li F, Li C . LncRNA FOXD2-AS1 Functions as a Competing Endogenous RNA to Regulate TERT Expression by Sponging miR-7-5p in Thyroid Cancer. Front Endocrinol (Lausanne). 2019; 10:207. PMC: 6463795. DOI: 10.3389/fendo.2019.00207. View

Wang S, Zhang S, He Y, Huang X, Hui Y, Tang Y . HOXA11-AS regulates JAK-STAT pathway by miR-15a-3p/STAT3 axis to promote the growth and metastasis in liver cancer. J Cell Biochem. 2019; 120(9):15941-15951. DOI: 10.1002/jcb.28871. View

Liang T, Zhou B, Shi L, Wang H, Chu Q, Xu F . lncRNA promotes proliferation and suppresses differentiation of myoblasts in skeletal muscle development by attenuating the function of miR-30c. FASEB J. 2017; 32(1):377-389. DOI: 10.1096/fj.201700560RR. View

Zhou L, Sun K, Zhao Y, Zhang S, Wang X, Li Y . Linc-YY1 promotes myogenic differentiation and muscle regeneration through an interaction with the transcription factor YY1. Nat Commun. 2015; 6:10026. DOI: 10.1038/ncomms10026. View

Shi X, Bowlin K, Garry D . Fhl2 interacts with Foxk1 and corepresses Foxo4 activity in myogenic progenitors. Stem Cells. 2009; 28(3):462-9. DOI: 10.1002/stem.274. View

Shi X, Wallis A, Gerard R, Voelker K, Grange R, DePinho R . Foxk1 promotes cell proliferation and represses myogenic differentiation by regulating Foxo4 and Mef2. J Cell Sci. 2012; 125(Pt 22):5329-37. PMC: 3561855. DOI: 10.1242/jcs.105239. View

10.

Schmitt A, Chang H . Long Noncoding RNAs in Cancer Pathways. Cancer Cell. 2016; 29(4):452-463. PMC: 4831138. DOI: 10.1016/j.ccell.2016.03.010. View

11.

Buckingham M, Rigby P . Gene regulatory networks and transcriptional mechanisms that control myogenesis. Dev Cell. 2014; 28(3):225-38. DOI: 10.1016/j.devcel.2013.12.020. View

12.

Jin J, Lv W, Xia P, Xu Z, Zheng A, Wang X . Long noncoding RNA regulates myogenesis by interacting with polycomb repressive complex 2. Proc Natl Acad Sci U S A. 2018; 115(42):E9802-E9811. PMC: 6196504. DOI: 10.1073/pnas.1801471115. View

13.

Sarropoulos I, Marin R, Cardoso-Moreira M, Kaessmann H . Developmental dynamics of lncRNAs across mammalian organs and species. Nature. 2019; 571(7766):510-514. PMC: 6660317. DOI: 10.1038/s41586-019-1341-x. View

14.

Yu X, Zhang Y, Li T, Ma Z, Jia H, Chen Q . Long non-coding RNA Linc-RAM enhances myogenic differentiation by interacting with MyoD. Nat Commun. 2017; 8:14016. PMC: 5241866. DOI: 10.1038/ncomms14016. View

15.

Xu S, Wang P, Zhang J, Wu H, Sui S, Zhang J . Ai-lncRNA EGOT enhancing autophagy sensitizes paclitaxel cytotoxicity via upregulation of ITPR1 expression by RNA-RNA and RNA-protein interactions in human cancer. Mol Cancer. 2019; 18(1):89. PMC: 6471868. DOI: 10.1186/s12943-019-1017-z. View

16.

Wang Z, Zhang X, Ji Y, Zhang P, Deng K, Gong J . The long noncoding RNA Chaer defines an epigenetic checkpoint in cardiac hypertrophy. Nat Med. 2016; 22(10):1131-1139. PMC: 5053883. DOI: 10.1038/nm.4179. View

17.

Zhang W, Wu Y, Hou B, Wang Y, Deng D, Fu Z . A SOX9-AS1/miR-5590-3p/SOX9 positive feedback loop drives tumor growth and metastasis in hepatocellular carcinoma through the Wnt/β-catenin pathway. Mol Oncol. 2019; 13(10):2194-2210. PMC: 6763786. DOI: 10.1002/1878-0261.12560. View

18.

Duan H, Li X, Chen Y, Wang Y, Li Z . LncRNA RHPN1-AS1 promoted cell proliferation, invasion and migration in cervical cancer via the modulation of miR-299-3p/FGF2 axis. Life Sci. 2019; 239:116856. DOI: 10.1016/j.lfs.2019.116856. View

19.

Gong C, Li Z, Ramanujan K, Clay I, Zhang Y, Lemire-Brachat S . A long non-coding RNA, LncMyoD, regulates skeletal muscle differentiation by blocking IMP2-mediated mRNA translation. Dev Cell. 2015; 34(2):181-91. DOI: 10.1016/j.devcel.2015.05.009. View

20.

Liu G, Zhao X, Zhou J, Cheng X, Ye Z, Ji Z . LncRNA TP73-AS1 Promotes Cell Proliferation and Inhibits Cell Apoptosis in Clear Cell Renal Cell Carcinoma Through Repressing KISS1 Expression and Inactivation of PI3K/Akt/mTOR Signaling Pathway. Cell Physiol Biochem. 2018; 48(1):371-384. DOI: 10.1159/000491767. View