Ssc-miR-21-5p regulates endometrial epithelial cell proliferation, apoptosis and migration via the PDCD4/AKT pathway

Hua, Renwu; Zhang, Xiuling; Li, Wenchao; Lian, Weisi; Liu, Qiaorui; Gao, Dengying; Wang, Yueying; Lei, Minggang

doi:10.1242/jcs.248898

Cited by 16 publications

(17 citation statements)

References 50 publications

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“…Reduced levels of miR-21 occur simultaneously with increased levels of PDCD4 protein. PDCD4 can induce apoptosis through its role in the AKT pathway [ 57 ]. miR-21 inhibition in endometrial cells increased PDCD4 expression which inhibited AKT phosphorylation; without active AKT, cell proliferation was repressed, and migration of endometrial cells was inhibited [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

“…PDCD4 can induce apoptosis through its role in the AKT pathway [ 57 ]. miR-21 inhibition in endometrial cells increased PDCD4 expression which inhibited AKT phosphorylation; without active AKT, cell proliferation was repressed, and migration of endometrial cells was inhibited [ 57 ]. Another study describes PDCD4 involvement in the JNK signaling pathway with their pro-apoptotic activity [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

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BPA Decreases PDCD4 in Bovine Granulosa Cells Independently of miR-21 Inhibition

Sabry

Williams

Werry

et al. 2022

IJMS

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microRNAs (miRNAs) are susceptible to environmental factors that might affect cellular function and impose negative effects on female reproduction. miR-21 is the most abundant miRNA in bovine granulosa cells and is widely reported as affected by Bisphenol A (BPA) exposure, yet the cause and consequences are not entirely elucidated. BPA is a synthetic endocrine disruptor associated with poor fertility. miR-21 function in bovine granulosa cells is investigated utilizing locked nucleic acid (LNA) oligonucleotides to suppress miR-21. Before measuring apoptosis and quantifying miR-21 apoptotic targets PDCD4 and PTEN, transfection was optimized and validated. BPA was introduced to see how it affects miR-21 regulation and which BPA-mediated effects are influenced by miR-21. miR-21 knockdown and specificity against additional miRNAs were confirmed. miR-21 was found to have antiapoptotic effects, which could be explained by its effect on the proapoptotic target PDCD4, but not PTEN. Previous findings of miR-21 overexpression were validated using BPA treatments, and the temporal influence of BPA on miR-21 levels was addressed. Finally, BPA effects on upstream regulators, such as VMP1 and STAT3, explain the BPA-dependent upregulation of miR-21 expression. Overall, this research enhances our understanding of miR-21 function in granulosa cells and the mechanisms of BPA-induced reproductive impairment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

BPA Decreases PDCD4 in Bovine Granulosa Cells Independently of miR-21 Inhibition

Sabry

Williams

Werry

et al. 2022

IJMS

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“…Overexpressed miR-21 in mesenchymal stem cells can improve ovarian structure and function by inhibiting granulosa cells apoptosis, thereby repairing chemotherapy-induced premature ovarian failure [ 12 ]. Knockdown of ssc-miR-21-5p inhibited proliferation and migration of endometrial epithelial cells (EECs), and induced their apoptosis [ 13 ]. In spermatogonial stem cell (SSCs), transient inhibition of miR-21 increased the number of germ cells undergoing apoptosis, suggesting that it has a role in maintaining SSC self-renewal [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Ssc-MiR-21-5p and Ssc-MiR-615 Regulates the Proliferation and Apoptosis of Leydig Cells by Targeting SOX5

Tang

Zhang

Yue

et al. 2022

Cells

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Leydig cells (LCs) are the predominant cells of androgen production, which plays key roles in spermatogenesis and maintaining male secondary sexual characteristics. Abnormal development of LCs affects androgen levels in vivo, affects fertility and may even lead to infertility. Little is known about the regulation mechanism on LCs’ development and maturation in domestic animals, especially the regulation of non-coding RNAs. In this study, we continued to dig deeper in the previous RNA-seq data of porcine LCs from our group, combined with detecting the expression profiles in different tissues and different types of cells in the testis, to screen out candidate microRNAs (miRNAs) that may affect the regulation of LCs. A total of two miRNAs, ssc-miR-21-5p and ssc-miR-615 (“ssc” is omitted below), were finally determined. After overexpression and interference of miRNAs in vitro, the effects of candidate miRNAs on the proliferation and apoptosis of TM3 (mouse Leydig cell line) were explored. The results showed that miR-21-5p led to a decrease in TM3 cell density and p53 (apoptosis related protein) expression. Meanwhile, miR-21-5p decreased EdU positive cell numbers, but increased TUNEL positive cell numbers, suggesting miR-21-5p could inhibit proliferation and promote apoptosis. Conversely, miR-615 could increase TM3 cell density. Western blot and TUNEL assay indicated miR-615 inhibited apoptosis, but had no effect on proliferation. In addition, Sox5 was identified a potential target gene of these two miRNAs by Dual-Luciferase reporter system assay. Our findings about functions of miRNAs in TM3 and the mapping of miRNAs-target gene regulatory network would provide an important basis for the further elucidation of miRNAs in regulating pig LCs.

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“…It is challenging to conduct in vivo tests in pigs, so we used six mice as the mouse implantation model after referring to other studies which focused on pig implantation [ 25 ]. The day of discovery of the vaginal suppository after intercourse is specified as the first day of pregnancy.…”

Section: Methodsmentioning

confidence: 99%

Circ0001470 Acts as a miR-140-3p Sponge to Facilitate the Progression of Embryonic Development through Regulating PTGFR Expression

Zhang

Zhou

Jiang

et al. 2022

Cells

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Embryonic implantation and development are vital in early pregnancy and assisted reproduction. Circular RNAs (circRNAs) are involved in the two physiological processes and thus regulate animal reproduction. However, their specific regulatory functions and mechanisms remain unclear. Here, a novel circ0001470, originating from the porcine GRN gene, differentially expressed on day 18 versus day 32 of gestation in Meishan and Yorkshire pigs was screened. The circularization characteristic of circ0001470 was identified based on divergent primer amplification, Sanger sequencing, RNase digestion, and RNA nuclear-cytoplasmic fractionation. Functionally, circ0001470 can promote cell proliferation and cycle progression of endometrial epithelial cells (EECs) and also inhibit apoptosis of EECs using CCK-8 assays and flow cytometry analyses. Mechanistically, bioinformatics database prediction, luciferase screening, RNA immunoprecipitation (RIP), RNA-pull down, and FISH co-localization experiments revealed that the circ0001470 acted as a competing endogenous RNA (ceRNA) through sponging miR-140-3p to regulate downstream PTGFR expression. Moreover, in vivo assays revealed that mmu_circGRN promoted embryonic development by affecting the expression of PTGFR, which can activate the MAPK reproduction pathway and facilitate pregnancy maintenance. This study enriched our understanding of circRNAs in embryo implantation and development by deciding the fate of EECs.

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Ssc-miR-21-5p regulates endometrial epithelial cell proliferation, apoptosis and migration via the PDCD4/AKT pathway

Cited by 16 publications

References 50 publications

BPA Decreases PDCD4 in Bovine Granulosa Cells Independently of miR-21 Inhibition

BPA Decreases PDCD4 in Bovine Granulosa Cells Independently of miR-21 Inhibition

Ssc-MiR-21-5p and Ssc-MiR-615 Regulates the Proliferation and Apoptosis of Leydig Cells by Targeting SOX5

Circ0001470 Acts as a miR-140-3p Sponge to Facilitate the Progression of Embryonic Development through Regulating PTGFR Expression

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