C/EBPα promotes porcine pre-adipocyte proliferation and differentiation via mediating MSTRG.12568.2/FOXO3 trans-activation for STYX

Weimin Lin; Lei Chen; Wenjing Meng; Kai Yang; Shengjuan Wei; Wei Wei; Jie Chen; Lifan Zhang

doi:10.1016/j.bbalip.2022.159206

C/EBPα promotes porcine pre-adipocyte proliferation and differentiation via mediating MSTRG.12568.2/FOXO3 trans-activation for STYX

Biochim Biophys Acta Mol Cell Biol Lipids. 2022 Oct;1867(10):159206. doi: 10.1016/j.bbalip.2022.159206. Epub 2022 Jul 21.

Authors

Weimin Lin¹, Lei Chen², Wenjing Meng², Kai Yang², Shengjuan Wei², Wei Wei², Jie Chen², Lifan Zhang³

Affiliations

¹ College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China; Sanya Institute of Nanjing Agricultural University, Sanya, Hainan 572024, China; College of Animal Science, Fujian Agriculture & Forestry University, Fuzhou, Fujian 350002, China.
² College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China.
³ College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China; Sanya Institute of Nanjing Agricultural University, Sanya, Hainan 572024, China. Electronic address: lifanzhang@njau.edu.cn.

PMID: 35870701
DOI: 10.1016/j.bbalip.2022.159206

Abstract

As a key adipogenic marker, C/EBPα (CCAAT/enhancer binding protein α) is also an important factor in regulating targets containing CCAAT element for transcription, whose products include coding and non-coding RNAs (ncRNAs). However, knowledge of the mechanism of C/EBPα affecting pre-adipocyte proliferation and adipogenesis through regulating ncRNA is still limited. In this study, we firstly conducted an investigation concerning the impact of C/EBPα knockdown on porcine pre-adipocytes by using RNA sequencing (RNA-Seq) to identify the role of key ncRNAs, especially lncRNAs and their correlated mRNAs in regulating proliferation and differentiation of porcine pre-adipocytes. 97 differentially expressed (DE) mRNAs and 4 DE lncRNAs were identified in si-C/EBPα groups compared with the si-NC groups. Meanwhile, we found C/EBPα directly target the promoter of a novel lncRNA, namely MSTRG.12568.2, which was trans-correlated with STYX (serine/threonine/tyrosine interacting protein), an important candidate gene for regulating cell proliferation. Moreover, FOXO3 (forkhead box O3) was identified as a co-regulator with MSTR.12568.2 for STYX. Overexpression and knockdown of any of the MSTRG.12568.2, STYX, and FOXO3 increased and decreased the levels of pre-adipocyte proliferation and differentiation, respectively, which demonstrated that they played a positive role in adipogenesis of pre-adipocytes. Furthermore, our results revealed that FOXO3 was necessary for MSTRG.12568.2 to trans-activate STYX. We revealed that C/EBPα regulated pre-adipocyte proliferation and differentiation through mediating trans-activation of MSTRG.12568.2-FOXO3 to STYX. These results provide a novel regulation signal for C/EBPα to influence porcine pre-adipocyte proliferation and differentiation and greatly benefit to our understanding of molecular mechanism regulating subcutaneous adipogenesis.

Keywords: Adipogenesis; C/EBPα; FOXO3; STYX; Trans-activate; lncRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes / metabolism
Adipogenesis / genetics
Animals
CCAAT-Enhancer-Binding Protein-alpha* / genetics
CCAAT-Enhancer-Binding Protein-alpha* / metabolism
Cell Proliferation
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
RNA, Messenger / metabolism
Swine

Substances

CCAAT-Enhancer-Binding Protein-alpha
RNA, Long Noncoding
RNA, Messenger