Sp1-Mediated circRNA circHipk2 Regulates Myogenesis by Targeting Ribosomal Protein Rpl7

Abstract

Circular RNAs (circRNAs) represent a class of covalently closed single-stranded RNA molecules that are emerging as essential regulators of various biological processes. The circRNA circHipk2 originates from exon 2 of the Hipk2 gene in mice and was reported to be involved in acute promyelocytic leukemia and myocardial injury. However, the functions and mechanisms of circHipk2 in myogenesis are largely unknown. Here, to deepen our knowledge about the role of circHipk2, we studied the expression and function of circHipk2 during skeletal myogenesis. We found that circHipk2 was mostly distributed in the cytoplasm, and dynamically and differentially expressed in various myogenesis systems in vitro and in vivo. Functionally, overexpression of circHipk2 inhibited myoblast proliferation and promoted myotube formation in C2C12 cells, whereas the opposite effects were observed after circHipk2 knockdown. Mechanistically, circHipk2 could directly bind to ribosomal protein Rpl7, an essential 60S preribosomal assembly factor, to inhibit ribosome translation. In addition, we verified that transcription factor Sp1 directly bound to the promoter of circHipk2 and affected the expression of Hipk2 and circHipk2 in C2C12 myoblasts. Collectively, these findings identify circHipk2 as a candidate circRNA regulating ribosome biogenesis and myogenesis proliferation and differentiation.

GATA1 regulates the microRNA‑328‑3p/PIM1 axis via circular RNA ITGB1 to promote renal ischemia/reperfusion injury in HK‑2 cells

“…For example, it has been shown that transcription factor YY1 can bind to the promoter of circ-ZNF609 and regulate the progression in cholangiocarcinoma ( 47 ). The promoter of circHipk2 has also been found to be regulated by transcription factor Sp1 and circHipk2 is regarded as an important candidate regulating myogenesis ( 48 ). The transcriptional activity of circITGB1 derives from the main promoter region upstream of ITGB1 coding sequence, which includes several transcription factor binding sites ( 46 ).…”

LMX1B Activated Circular RNA GFRA1 Modulates the Tumorigenic Properties and Immune Escape of Prostate Cancer

“…For instance, circRNA ARF1 expression in glioma stem cells is regulated by U2AF2 [33]. circRNA circHipk2 expression in C2C12 myoblasts is mediated by Sp1 [34], and circ-FOXP1 in hepatocellular carcinoma cells is regulated by SOX9 [9][10][11]. Therefore, we investigated the upstream regulator of circGFRA1 in PCa cells showing that circGFRA1 is regulated by LMX1B, which has previously been shown to be involved in many cancers, including ovarian, esophageal, and glioma [35][36][37].…”

Coordinated transcriptional and post-transcriptional epigenetic regulation during skeletal muscle development and growth in pigs

“…DNA 5-methylcytosine (5mC) and RNA N6-methyladenosine (m 6 A) are two typical epigenetic modifications that play essential roles in transcription and post-transcription regulation, respectively [ 9 – 11 ]. Recently, many studies have explored the epigenetic mechanisms underlying skeletal muscle growth and development in mammals, including chromatin landscape [ 12 , 13 ], microRNA [ 14 , 15 ], circRNA [ 16 , 17 ], DNA and histone modifications [ 14 , 18 ]. The discovery of the RNA methylation system in post-transcriptional regulation of myoblast differentiation and proliferation provides another layer of information for understanding skeletal muscle development and growth [ 19 , 20 ].…”