Molecular network of miR-1343 regulates the pluripotency of porcine pluripotent stem cells via repressing OTX2 expression

Abstract

2019) Molecular network of miR-1343 regulates the pluripotency of porcine pluripotent stem cells via repressing OTX2 expression, RNA Biology, 16:1, 82-92, ABSTRACTPorcine OTX2 was found to be highly activated in porcine iPS cells (piPSCs) that were reported by different laboratories worldwide. To reveal the regulatory function of OTX2 in porcine reprogrammed cells, we screened porcine miRNA-seq databases and found two miRNAs, miR-1343 and miR-545, that could specifically bind to 3ʹUTR of OTX2 and suppress endogenous OTX2 expression in piPSCs. Knockdown of OTX2 by miR-1343 and miR-545 could significantly increase the expression of SOX2 and ESRRB, but did not alter the expressions of OCT4 and KLF4, and improve the pluripotency of piPSCs. The promoter-based assays showed that OTX2 potentially bound to the promoter region of SOX2 and ESRRB and suppressed their expression. On the other hand, SOX2 could interact with OTX2 promoter. Ectopic expression of SOX2 could significantly decrease OTX2 promoter activity, showing that there is a negative feedback loop between SOX2 and OTX2. Additionally, SOX2 and ESRRB significantly stimulated miR-1343 expression in piPSCs, but OTX2 down regulated the expression of miR-1343 in either direct or indirect manners. In summary, this study demonstrates that there is a regulatory network mediated by miR-1343, in which downregulation of OTX2 by miR-1343 can elevate the expression of pluripotent genes that were then sustain the pluripotency of piPSCs. ARTICLE HISTORY

Genome-wide analysis of circular RNA-mediated ceRNA regulation in porcine skeletal muscle development

“…In the ovaries of highly fertile sows, miR-1343 suppresses expression of transforming growth factor-β receptor type 1 (TGFBR1) to inhibit pig granule cell proliferation and promote apoptosis, thus affecting sow fecundity [72]. Furthermore, miR-1343 specifically binds to the 3´UTR of Orthodenticle homeobox 2 (OTX2) and inhibits endogenous OTX2 expression in pig pluripotent stem cells (piPSCs), enhancing the expression of pluripotency genes and thus maintaining piPSCs pluripotency in pigs [73]. Finally, we chose to focus specifically on PGM1, which has the highest expression level in porcine longissimus dorsi and biceps femoris.…”

Competitive endogenous RNA network reveals that miR-1343 play key regulatory roles in longissimus dorsi muscle between Saba and Yorkshire pigs

“…MicroRNA miR-1343 has so far been identified to play roles in regulating the fibrosis of human and the pluripotency of porcine pluripotent stem cells [49,50], and some studies showed that miR-1343 was related with the susceptible to porcine reproductive and respiratory syndrome (PRRS) and pig backfat formation [51,52]. So far, no studies clearly reported the function of miR-1343 in pork quality formation.…”

Enhancement of Chromatin and Epigenetic Reprogramming in Porcine SCNT Embryos—Progresses and Perspectives

“…Studies in pigs revealed that miRNAs, including miR-1343, miR-302, miR-302b and miR-200 , are involved in the acquisition and maintenance of cell pluripotency by regulating the expression of TFs, such as SOX2 and OCT-4 ( Ma et al, 2014 ; Qiao et al, 2019 ; Xie et al, 2019 ). However, the impact of miRNAs during cell reprogramming and development of pig SCNT embryos has not been extensively explored.…”