miR-202-3p Regulates Sertoli Cell Proliferation, Synthesis Function, and Apoptosis by Targeting LRP6 and Cyclin D1 of Wnt/β-Catenin Signaling

Yang, Chao; Yao, Chencheng; Tian, Ruhui; Zhu, Zijue; Zhao, Liangyu; Li, Peng; Chen, Huixing; Huang, Yuhua; Zhi, Erlei; Gong, Yuehua; Xue, Yi; Wang, Hong; Yuan, Quan; He, Zuping

doi:10.1016/j.omtn.2018.10.012

Cited by 59 publications

(30 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By cascading with the Wnt/β-catenin signaling, this gene plays a prominent role in regulating cell differentiation, proliferation, migration, as well as the deterioration of diverse cancer types, including RB [15,16]. Furthermore, it has been reported that the expression level of LRP6 is modulated by a plurality of miRNAs, such as miR-202-3p and miR-126-3p [17,18]. However, the mechanism which is responsible for the dysregulation of LRP6 expression in RB has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Circ_0000527 promotes the progression of retinoblastoma by regulating miR-646/LRP6 axis

Zhang¹,

Wu²,

Li³

et al. 2020

Cancer Cell Int

View full text Add to dashboard Cite

Background: Researches validate that circular RNAs (circRNAs) are dysregulated in a variety of malignancies and play an important role in regulating the malignant phenotype of tumor cells. Nevertheless, the role of circ_0000527 in retinoblastoma (RB) and its regulatory mechanisms remain largely unknown. Methods: Real-time PCR (RT-PCR) was used to detect circ_0000527 and miR-646 expression in RB tissues and cells. The LRP6 expression in RB cells was detected by Western blot. The relationship between circ_0000527 expression and the clinicopathological parameters of RB patients was analyzed. Cell proliferation, apoptosis and metastasis were monitored by cell counting kit-8 (CCK-8), flow cytometry, and Transwell assay. The dual-luciferase reporter gene assay and RIP assay were employed to verify the targeting relationship between circ_0000527 and miR-646, miR-646 and LRP6. Results: Circ_0000527 was highly expressed in both RB and RB cell lines, whose high expression level and degree of differentiation were significantly correlated with the increase in cTNM staging level. Overexpression of circ_0000527 contributed to RB cell proliferation, migration, invasion and suppressed cell apoptosis, while knocking down circ_0000527 inhibited the above malignant biological behavior. The underlying mechanism suggested that functioning as a endogenous competitive RNA, circ_0000527 directly targeted miR-646 and positively regulated LRP6 expression. Conclusion: Circ_0000527 enhances the proliferation and metastasis of RB cells by modulating the miR-646/LRP6 axis.

show abstract

Section: Introductionmentioning

confidence: 99%

Circ_0000527 promotes the progression of retinoblastoma by regulating miR-646/LRP6 axis

Zhang¹,

Wu²,

Li³

et al. 2020

Cancer Cell Int

View full text Add to dashboard Cite

show abstract

“…In male mice, miR-34b/c and − 449a/b/c led to sperm aggregation and agglutination, luminal obstruction, and sperm granulomas in male mice (32). In Sertoli cells, the miR-202-3p controls the apoptosis via targeting LRP6 and Cyclin D1 of the Wnt/β-catenin signaling pathway (33). Humans found that several kinds of environmental chemicals, including SiNPs, could alter the expressions of miRNAs (34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

Silica nanoparticles inducing the apoptosis of spermatocyte cell through microRNA-450b-3p targeting MTCH2-mediating mitochondrial signaling pathway

Zhou

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Silica nanoparticles (SiNPs) are found in environmental particulate matter and are proven to have adverse effects on fertility. The relationship and underlying mechanisms between miRNAs and apoptosis induced by SiNPs during spermatogenesis is currently ambiguous. Experimental design: The present study was designed to investigate the role of miRNA-450b-3p in the reproductive toxicity caused by SiNPs. In vivo, 40 male mice were randomly divided into control and SiNPs groups, 20 per group. The mice in the SiNPs group were administrated 20 mg/kg SiNPs by tracheal perfusion once every 5 days, for 35 days, and the control group were given the equivalent of a normal luminal saline. In vitro, spermatocyte cells were divided into 0 and 5 μg/mL SiNPs groups, after passaged for 30 generations, the GC-2spd cells in 5 μg/mL SiNPs groups were transfected with miRNA-450b-3p and its mimic and inhibitor. Results: In vivo, the results showed that SiNPs damaged tissue structures of testis, decreased the quantity and quality of the sperm, reduced the expression of miR-450b-3p, and increased the protein expressions of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, and Caspase-3 in the testis. In vitro, SiNPs obviously repressed the viability and increased the LDH level and apoptosis rate, decreased the levels of the miR-450b-3p, significantly enhanced the protein expressions of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, Caspase-3; while the mimic of miR-450b-3p reversed the changes induced by SiNPs, but inhibitor further promoted the effects induced by SiNPs.Conclusion: The result suggested that SiNPs could induce the spermatocyte apoptosis by inhibiting the miR-450b-3p expression to target promoting the MTCH2 resulting in activating mitochondrial apoptotic signaling pathways in the spermatocyte cells.

show abstract

“…KS Sertoli cells were isolated by sequential two-step enzyme digestion as described in our previous study (Yang et al 2019). Briefly, testicular tissues were enzymatically digested with 4 mg/ml collagenase type IV for 5 min to remove most interstitial cells (such as Leydig cells and PTM cells); then, the tissues were digested with 4 mg/ml collagenase type IV, 2.5 mg/ml hyaluronidase, and 1 mg/ml trypsin at 37°C for 20 min to isolate the remaining tissue as single cells.…”

Section: Methodsmentioning

confidence: 99%

Low XIST expression in Sertoli cells of Klinefelter syndrome patients caused the high susceptibility of these cells to an extra X chromosome

Zhao

Yao

Xing

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Klinefelter syndrome (KS) is the most common genetic cause of human male infertility. Patients suffer from heterogeneous testicular atrophy with loss of both germ cells and Sertoli cells. However, the mechanism by which the extra X chromosome causes failure of spermatogenesis remains poorly understood. Here, we profiled testicular single-cell transcriptomes from three KS patients and compared the results with those of healthy donors. Among different somatic cells, Sertoli cells showed the greatest changes in KS patients. Further analysis showed that XIST, a key long intergenic non-coding RNA that inactivates one X chromosome in female mammals, was widely expressed in somatic cells, except for Sertoli cells, leading to an increase in X-inactivation genes in these cells, which may cause Sertoli cells death and disruption of the spermatogenic microenvironment. Our study proposed a new mechanism to explain the unique pathological manifestations of KS in the testes and provided a theoretical basis for subsequent research and related treatment.

show abstract

miR-202-3p Regulates Sertoli Cell Proliferation, Synthesis Function, and Apoptosis by Targeting LRP6 and Cyclin D1 of Wnt/β-Catenin Signaling

Cited by 59 publications

References 79 publications

Circ_0000527 promotes the progression of retinoblastoma by regulating miR-646/LRP6 axis

Circ_0000527 promotes the progression of retinoblastoma by regulating miR-646/LRP6 axis

Silica nanoparticles inducing the apoptosis of spermatocyte cell through microRNA-450b-3p targeting MTCH2-mediating mitochondrial signaling pathway

Low XIST expression in Sertoli cells of Klinefelter syndrome patients caused the high susceptibility of these cells to an extra X chromosome

Contact Info

Product

Resources

About