MicroRNA-142-3p suppresses endometriosis by regulating KLF9-mediated autophagy <i>in vitro</i> and <i>in vivo</i>

Ma, Lin; Li, Zaiyi; Li, Weihao; Ai, Jing; Chen, Xiaoxuan

doi:10.1080/15476286.2019.1657352

Cited by 41 publications

(34 citation statements)

References 54 publications

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“…The described effects of miR-142-3p might be similar across more cell types, as our laboratory has previously shown that miR-142-3p also decreases cell area and migration in breast cancer cell lines [22]. Similar effects of miR-142-3p on migration in endometrial stromal cells were previously observed by Ma and colleagues [2], who attributed these observations to the miR-142-3p effect on KLF9 and VEGFA expression. However, none of our used databases predicted KLF9 as a miR-142-3p Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 17 July 2020 doi:10.20944/preprints202007.0399.v1…”

Section: Discussionsupporting

confidence: 75%

“…Therefore, additional targets may have contributed to the functional impact of this miRNA in our functional assay. Finally, wound healing studies in miR-142-3p mice [23] and retroviral delivery studies in an in vivo model of endometriosis [2] suggest that confirmation of our findings in more complex in vivo models of endometriosis may be worthwhile.…”

Section: Discussionmentioning

confidence: 58%

“…This could be due to several factors, including altered microRNA expression and its associated posttranscriptional regulation of microRNA targets in the ectopic milieu [17] [18] [19]. One microRNA gene that is down-regulated at ectopic locations and might thus contribute to these phenotypic changes is the microRNA-142-3p [1] [2]. However, the exact role microRNA-142-3p plays in the pathophysiology of endometriosis currently remains incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

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miR-142-3p Reduces the Size, Migration and Contractility of Endometrial and Endometriotic Stromal Cells by Targeting Integrin- and Rho GTPase-related Pathways that Regulate Cytoskeletal Function

Börschel¹,

Stejskalová²,

Schäfer³

et al. 2020

Preprint

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Downregulated microRNA-142-3p signaling contributes to the pathogenesis of endometriosis [1] [2], an invasive disease where the lining of the uterus grows at ectopic locations, by yet incompletely understood mechanisms. Using bioinformatics and in vitro assays, this study identifies cytoskeletal regulation and integrin signaling as two relevant categories of miR-142-3p targets. qPCR revealed that miR-142-3p upregulation in St-T1b cells downregulates ROCK2, CFL2, RAC1, WASL and ITGAV. qPCR and Western-blotting showed miR-142-3p effect on WASL and ITGAV was significant also in primary endometriotic stroma cells. Luciferase reporter assays in ST-T1b cells then confirmed direct regulation of ITGAV and WASL. On the functional side, miR-142-3p upregulation significantly reduced ST-T1b cell size, the size of vinculin plaques, migration through fibronectin-coated transwell filters and the ability of ST-T1b and primary endometriotic stroma cells to contract collagen I gels. These results suggest that miR-142-3p has a strong mechanoregulatory effect on endometrial stroma cells and its external administration reduces the invasive endometrial phenotype. Within the limits of an in vitro investigation, our study provides new mechanistic insights into the pathogenesis of endometriosis and provides a perspective for the development of miR-142-3p based drugs for inhibiting invasive growth of endometriotic cells.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

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miR-142-3p Reduces the Size, Migration and Contractility of Endometrial and Endometriotic Stromal Cells by Targeting Integrin- and Rho GTPase-related Pathways that Regulate Cytoskeletal Function

Börschel¹,

Stejskalová²,

Schäfer³

et al. 2020

Preprint

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show abstract

“…For example, Jia et al reported that miR-17-5p, miR-20a and miR-22 are downregulated in plasma samples from patients with Ems, and investigated their prognostic value (20). Ma et al observed that injection of miR-142-3p significantly attenuated ectopic endometriotic lesions in vivo (34). Li et al also found that miR-451a inhibition reduced established Ems lesions in a murine model (35).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑16 inhibits endometrial stromal cell migration and invasion through suppression of the inhibitor of nuclear factor‑κB kinase subunit β/nuclear factor‑κB pathway

Wang

Ren²,

Shao

et al. 2020

Int J Mol Med

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Accumulating evidence has demonstrated that endometrial stromal cells (EScs) are responsible for the pathogenesis of endometriosis (Ems), which is characterized by the presence of functional endometrial-like tissues outside the uterine cavity. Abnormal expression of microRNAs (miRNAs) in EScs may be implicated in the etiology of Ems; however, the exact mechanisms have yet to be fully elucidated. The aim of the present study was to investigate the effects of miRNAs on EScs and the underlying mechanisms. Using a microarray assay, microRNA-16 (miR-16) was found to be significantly downregulated in the ectopic endometrial tissues in patients with Ems, compared with that in eutopic endometrial tissues. Overexpression of miR-16 significantly suppressed the migration and invasion of EScs, whereas miR-16 inhibition exerted the opposite effects. Furthermore, dual luciferase reporter assay demonstrated that miR-16 directly targeted the inhibitor of nuclear factor (NF)-κB kinase subunit β (IKKβ) and suppressed its translation. It was observed that the expression of IKKβ was upregulated and inversely correlated with miR-16 levels in the ectopic endometrial tissues in patients with Ems. Additionally, knockdown of IKKβ by si-IKKβ mimicked the effects of miR-16 overexpression on EScs, while the promoting effects of IKKβ overexpression on the migration and invasion of EScs were attenuated by miR-16 overexpression. Finally, miR-16 inhibited the activation of the NF-κB pathway by targeting IKKβ. collectively, these results demonstrated that miR-16 may suppress Ems by inhibiting the IKKβ/NF-κB pathway, suggesting that miR-16 may be a useful target in the treatment of Ems.

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“…This could be due to several factors, including altered microRNA expression and its associated post-transcriptional regulation of microRNA targets in the ectopic milieu [ 16 , 17 , 18 ]. One microRNA gene that is downregulated at ectopic locations and might thus contribute to these phenotypic changes is the microRNA-142-3p [ 5 , 19 ]. Two previous studies on the endometriotic cell line Hs832.Tc (ATCC CRL-7566) [ 19 ] and the endometrial stroma cell line ST-T1b [ 20 ] identified the transcriptional regulator KLF9 , the interleukin-6 receptor subunit IL6ST /gp130, and steroid sulfatase ( STS ) as regulatory targets of miR-142-3p, however, the exact role microRNA-142-3p plays in the pathophysiology of endometriosis currently remains incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

miR-142-3p Reduces the Size, Migration, and Contractility of Endometrial and Endometriotic Stromal Cells by Targeting Integrin- and Rho GTPase-Related Pathways That Regulate Cytoskeletal Function

et al. 2020

View full text Add to dashboard Cite

Downregulated microRNA-142-3p signaling contributes to the pathogenesis of endometriosis, an invasive disease where the lining of the uterus grows at ectopic locations, by yet incompletely understood mechanisms. Using bioinformatics and in vitro assays, this study identifies cytoskeletal regulation and integrin signaling as two relevant categories of miR-142-3p targets. qPCR revealed that miR-142-3p upregulation in St-T1b cells downregulates Rho-associated protein kinase 2 (ROCK2), cofilin 2 (CFL2), Ras-related C3 botulinum toxin substrate 1 (RAC1), neural Wiskott-Aldrich syndrome protein (WASL), and integrin α-V (ITGAV). qPCR and Western-blotting showed miR-142-3p effect on WASL and ITGAV was significant also in primary endometriotic stroma cells. Luciferase reporter assays in ST-T1b cells then confirmed direct regulation of ITGAV and WASL. On the functional side, miR-142-3p upregulation significantly reduced ST-T1b cell size, the size of vinculin plaques, migration through fibronectin-coated transwell filters, and the ability of ST-T1b and primary endometriotic stroma cells to contract collagen I gels. These results suggest that miR-142-3p has a strong mechanoregulatory effect on endometrial stroma cells and its external administration reduces the invasive endometrial phenotype. Within the limits of an in vitro investigation, our study provides new mechanistic insights into the pathogenesis of endometriosis and provides a perspective for the development of miR-142-3p based drugs for inhibiting invasive growth of endometriotic cells.

show abstract

MicroRNA-142-3p suppresses endometriosis by regulating KLF9-mediated autophagy in vitro and in vivo

Cited by 41 publications

References 54 publications

miR-142-3p Reduces the Size, Migration and Contractility of Endometrial and Endometriotic Stromal Cells by Targeting Integrin- and Rho GTPase-related Pathways that Regulate Cytoskeletal Function

miR-142-3p Reduces the Size, Migration and Contractility of Endometrial and Endometriotic Stromal Cells by Targeting Integrin- and Rho GTPase-related Pathways that Regulate Cytoskeletal Function

MicroRNA‑16 inhibits endometrial stromal cell migration and invasion through suppression of the inhibitor of nuclear factor‑κB kinase subunit β/nuclear factor‑κB pathway

miR-142-3p Reduces the Size, Migration, and Contractility of Endometrial and Endometriotic Stromal Cells by Targeting Integrin- and Rho GTPase-Related Pathways That Regulate Cytoskeletal Function

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