LncIRS1 controls muscle atrophy via sponging miR‐15 family to activate IGF1‐PI3K/AKT pathway

Abstract

Background Recent studies indicate important roles for long noncoding RNAs (lncRNAs) in the regulation of gene expression by acting as competing endogenous RNAs (ceRNAs). However, the specific role of lncRNAs in skeletal muscle atrophy is still unclear. Our study aimed to identify the function of lncRNAs that control skeletal muscle myogenesis and atrophy. Methods RNA sequencing was performed to identify the skeletal muscle transcriptome (lncRNA and messenger RNA) between hypertrophic broilers and leaner broilers. To study the ‘sponge’ function of lncRNA, we constructed a lncRNA‐microRNA (miRNA)‐gene interaction network by integrated our previous submitted skeletal muscle miRNA sequencing data. The primary myoblast cells and animal model were used to assess the biological function of the lncIRS1 in vitro or in vivo . Results We constructed a myogenesis‐associated lncRNA‐miRNA‐gene network and identified a novel ceRNA lncRNA named lncIRS1 that is specifically enriched in skeletal muscle. LncIRS1 could regulate myoblast proliferation and differentiation in vitro , and muscle mass and mean muscle fibre in vivo . LncIRS1 increases gradually during myogenic differentiation. Mechanistically, lncIRS1 acts as a ceRNA for miR‐15a, miR‐15b‐5p, and miR‐15c‐5p to regulate IRS1 expression, which is the downstream of the IGF1 receptor. Overexpression of lncIRS1 not only increased the protein abundance of IRS1 but also promoted phosphorylation level of AKT (p‐AKT) a central component of insulin‐like growth factor‐1 pathway. Furthermore, lncIRS1 regulates the expression of atrophy‐related genes and can rescue muscle atrophy. Conclusions The newly identified lncIRS1 acts as a sponge for miR‐15 family to regulate IRS1 expression, resulting in promoting skeletal muscle myogenesis and controlling atrophy.

LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway

“…Conversely, LINC00673 was identified to play a role in tumorigenesis in a variety of malignancies [11][12][13][14][15]. A rapidly growing number of studies have suggested that cytoplasmic lncRNAs are essential mediators of intracellular signaling pathways and are involved in regulating mRNA stabilization and transport as well as microRNA sponging [16][17][18]. Although LINC00673 has been implicated in the regulation of breast cancer cell metastasis via the modulation of epithelial-mesenchymal transition (EMT) in breast cancer [19], it remains to be seen whether LINC00673 acts as a competing endogenous RNA (ceRNA) to promote cell proliferation in breast cancer.…”

RNA-sequencing analysis reveals the potential contribution of lncRNAs in palmitic acid-induced insulin resistance of skeletal muscle cells

“…Similarly, the diverse mechanisms for modulating insulin sensitivity in skeletal muscle cells enable exploring how this candidate lncRNA regulated these genes from the co-expression network. Consistent with their predominantly in cytoplasmic localization, muscle-derived lncRNAs have been increasingly described as miRNA sponges with targeting downstream genes [69,70]. For example, muscle-enriched lncRNA H19 acted to enhance muscle insulin sensitivity like a sponge by sequestering let-7 targeting dual specificity phosphatase 27 (DUSP27) expression levels [68].…”

Long Non-Coding RNA H19 Promotes Porcine Satellite Cell Differentiation by Interacting with TDP43

“…For example, linc-RAM promotes the assembly of the MyoD-Baf60c-Brg1 complex on the regulatory elements of myogenic genes by directly binding MyoD [9]. In addition, lncIRS1 regulates IRS1 expression and promotes skeletal muscle myogenesis through acting as a sponge for the miR-15 family [10]. LncRNAs usually perform different functions depending on their subcellular localization.…”