MicroRNA-432 targeting E2F3 and P55PIK inhibits myogenesis through PI3K/AKT/mTOR signaling pathway

Abstract

Skeletal muscle is the dominant executant in locomotion and regulator in energy metabolism. Embryonic myogenesis and postnatal muscle growth are controlled by a cascade of transcription factors and epigenetic regulatory mechanisms. MicroRNAs (miRNAs), a family of non-coding RNA of 22 nucleotides in length, post-transcriptionally regulates expression of mRNA by pairing the seed sequence to 3 0 UTR of target mRNA. Increasing evidence has demonstrated that miRNAs are important regulators in diverse myogenic processes. The profiling of miRNA expression revealed that miR-432 is more enriched in the longissimus dorsi of 35-day-old piglets than that of adult pigs. Our gain of function study showed that miR-432 can negatively regulate both myoblast proliferation and differentiation. Mechanically, we found that miR-432 is able to down-regulate E2F transcription factor 3 (E2F3) to inactivate the expression of cell cycle and myogenic genes. We also identified that phosphatidylinositol 3-kinase regulatory subunit (P55PIK) is another target gene of miR-432 in muscle cells. downregulation of P55PIK by miR-432 leads to inhibition of P55PIK-mediated PI3K/AKT/mTOR signaling pathway during differentiation. The blocking effect of miR-432 on this pathway can be rescued by insulin treatment. Taken together, our findings identified microRNA-432 as a potent inhibitor of myogenesis which functions by targeting E2F3 and P55PIK in muscle cells.

MicroRNA‐323‐3p promotes myogenesis by targeting Smad2

“…The specific miRNA in skeletal muscle also regulates the proliferation and differentiation of myoblasts. An analysis of the miRNAs in longissimus dorsi of Rongchang pig revealed that miR‐323‐3p had significant expression changes in different age groups . Furthermore, miR‐323‐3p was highly expressed in muscle.…”

“…In our previous studies, we performed miRNA sequencing in longissimus dorsi muscle of Rongchang pigs in different age groups. 12 The data showed that miR-323-3p was differentially expressed in two age groups. The present research indicates that miR-323-3p inhibits proliferation and promotes differentiation by targeting Smad2 in myoblasts, and reveals that miR-323-3p functions as a negative regulator in myogenesis.…”

“…Studies have found that myogenic lineage progression is controlled by some myogenic regulatory factors (MRFs), mainly containing myogenic factor 5, myogenic differentiation (MyoD), and myogenin (MyoG) . Many other factors influence these MRFs, such as microRNAs (miRNAs), circular RNAs, and receptor proteins …”

“…It was reported that miR‐323‐3p was associated with diseases, such as cancer, cardiomyopathy, and lung injury, but its function in myogenesis is not clear. In our previous studies, we performed miRNA sequencing in longissimus dorsi muscle of Rongchang pigs in different age groups . The data showed that miR‐323‐3p was differentially expressed in two age groups.…”

“…9,10 Many other factors influence these MRFs, such as microRNAs (miRNAs), circular RNAs, and receptor proteins. [11][12][13][14][15][16] MiRNAs, a class of 21-nucleotide noncoding RNAs, regulate multiple biological processes. 17 MiRNAs regulate target genes by binding to the 3 ′ -untranslated region (3′-UTR) of messenger RNAs (mRNAs) to inhibit translation.…”