microRNA 92b-3p regulates primordial follicle assembly by targeting TSC1 in neonatal mouse ovaries

Abstract

The primordial follicle pool, providing all oocytes available to a female throughout her reproductive life, is established perinatally. The formation of primordial follicle pool is regulated by precise transcriptional and post-transcriptional mechanisms. Recent studies have identified several microRNAs as post-transcriptional regulatory factors in the process of primordial follicle assembly.Here, we showed that miR-92b-3p was significantly upregulated in the stage of primordial follicle assembly in newborn mouse ovaries. Inhibiting miR-92b-3p suppressed the formation of primordial follicles, while overexpression of miR-92b-3p accelerated the processes of cyst breakdown and the following primordial follicle assembly. Accordingly, the expression of follicular developmentrelated genes was reduced upon inhibiting of miR-92b-3p and increased under miR-92b-3p overexpression. Mechanistic studies identified TSC1 as a direct target of miR-92b-3p. miR-92b-3p could activate mTOR/Rps6 signaling through targeting and inhibiting TSC1 expression. In addition, knockdown of TSC1 showed an identical phenotype with that of miR-92b-3p overexpression in accelerating processes of cyst breakdown and primordial follicle formation. Thus, our work demonstrates that miR-92b-3p is a novel regulator of primordial follicle assembly by negatively regulating TSC1 in mTOR/Rps6 signaling. ARTICLE HISTORY

MiR‐92b‐3p regulates oxygen and glucose deprivation–reperfusion‐mediated apoptosis and inflammation by targeting TRAF3 in PC12 cells

“…For instance, miR‐92b‐3p down‐regulation prevents lung cancer cell growth via targeting reversion‐inducing‐cysteine‐rich protein with kazal motifs (RECK; Lei, Huang, & Gong, 2014). MiR‐92b‐3p targets tuberous sclerosis complex 1 (TSC1) to regulate primordial follicle assembly in neonatal mouse ovaries (Li et al., 2019). Phosphatase and tensin homologue (PTEN) and Smad7 are direct targets of miR‐92b‐3p in various cells (Li, Li et al., 2013; Song et al., 2016b; Wang et al., 2020).…”

Long non-coding RNA Xist regulates oocyte loss via suppressing miR-23b-3p/miR-29a-3p maturation and upregulating STX17 in perinatal mouse ovaries

“…Recent studies have demonstrated that nuclear lncRNA regulates miRNA expression by suppressing its maturation process in the nucleus 33 , 34 . Given that Xist is also a nuclear lncRNA and that miRNAs are essential to promote oocyte survival and decrease apoptosis 26 – 29 , we wondered whether Xist may also play such a role in regulating oocyte death during PF formation. Previous studies have profiled differentially expressed miRNAs for association with premature ovarian failure development in both animal models and patients, including miR-23b-3p and miR-29a-3p 35 , 36 .…”

“…The mature miRNA is finally generated once one strand is discarded. It is well acknowledged that miRNAs can negatively control the expression of target genes in a wide range of cell signaling pathways related to different physiological and pathological processes 24 , 25 , including PF formation and even POI 26 – 29 . However, these studies focus more on how these miRNAs regulate their downstream targets and participate in the regulation of PF formation, and reports of miRNA biogenesis and regulation are missing.…”

microRNAs Mediated Regulation of the Ribosomal Proteins and its Consequences on the Global Translation of Proteins

“…Another example is cardiac hypertrophy, which is suppressed in mice by miR-92b-3p, potentially by targeting MEF2D [ 250 ] and HAND2 [ 251 ]. Furthermore, it can inhibit the pulmonary artery derived smooth muscle cells proliferation by targeting USP28 [ 281 ], as well as regulate the assembly of primordial follicles in the ovaries of neonatal mice by targeting TSC1 [ 282 ]. In cancer, miR-92b-3p have both anti- and pro-cancer roles in different types of cancers: it suppresses pancreatic cancer by targeting GABRA3 [ 252 ], but promotes several others such as colorectal cancer by inhibiting FBXW7 [ 253 ], esophageal squamous cell carcinoma by target KLF4 and DCS2 [ 254 ], gastric cancer by downregulating MMP2, MMP9 and HOXD10 [ 255 ], and also could be a biomarker for synovial sarcoma [ 256 ].…”