MiR-27a promotes EMT in ovarian cancer through active Wnt/𝜷-catenin signalling by targeting FOXO1

Zhang, Liya; Chen, Yuan; Jia, Jue; Zhu, Xi; He, Yan; Wu, Liming

doi:10.3233/cbm-181229

Cited by 52 publications

(38 citation statements)

References 38 publications

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“…Ding et al showed that miR-27a antagomir injection inhibited the tumor growth of gastric cancer in a xenograft model [27]. In OC, miR-27a overexpression promoted the process of EMT through activating Wnt/β-catenin signaling pathway by targeting FOXO1 [17]. Thus, it was hypothesized that APS exhibits its anti-tumor effect through down-regulating miR-27a expression.…”

Section: Discussionmentioning

confidence: 99%

“…Among them, miR-27a was selected for further investigation as it was the most significantly up-regulated miRNA in the APS treatment group. Interestingly, miR-27a has been identified as oncogenic miRNA in OC, with marked effects on cell growth of OC cells [16][17][18]. Thus, we sought to determine the potential roles of miR-27a in the actions of APS in subsequent studies.…”

Section: Aps Down-regulated the Expression Of Mir-27a In Oc Cellsmentioning

confidence: 99%

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Astragalus polysaccharides inhibit ovarian cancer cell growth via microRNA-27a/FBXW7 signaling pathway

et al. 2020

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Astragalus polysaccharide (APS), a natural antioxidant found in Astragalus membranaceus emerging as a novel anticancer agent, exerts antiproliferative and pro-apoptotic activity in various cancer cell types, but its effect on ovarian cancer (OC) remains unknown. In the present study, we tried to elucidate the role and mechanism of APS in OC cells. Our results showed that APS treatment suppressed the proliferation and induced apoptosis in OC cells. Afterward, the microRNA (miRNA) profiles in APS-treated cells were determined by a microarray assay, and whether APS affected OV-90 cells through regulation of miRNA was determined. Among these aberrant miRNAs, miR-27a was selected for further study as its oncogenic roles in various human cancers. Moreover, we found overexpression of miR-27a reversed the antiproliferation and pro-apoptotic effects of APS on OC cells. F-box and WD-40 domain protein 7 (FBXW7), a classical tumor suppressor, was found directly targeted by miR-27a and its translation was suppressed by miR-27a in OC cells. Finally, it was also observed that knockdown of FBXW7 by si-FBXW7 reversed the tumor suppressive activity of APS in OC cells, which is similar to the effects of miR-27a overexpression. Our findings demonstrate that APS can suppress OC cell growth in vitro via miR-27a/FBXW7 axis, and this observation reveals the therapeutic potential of APS for treatment of OC.

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Section: Discussionmentioning

confidence: 99%

Section: Aps Down-regulated the Expression Of Mir-27a In Oc Cellsmentioning

confidence: 99%

Astragalus polysaccharides inhibit ovarian cancer cell growth via microRNA-27a/FBXW7 signaling pathway

et al. 2020

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“…In agreement with the oncogenic activities suggested by our data, miR‐27a has been accumulatively documented to be critically involved in multiple forms of human cancers so far. For example, Zhang et al . reported that miR‐27a promoted the EMT process in ovarian cancer via activation of Wnt/β‐catenin pathway through targeting FOXO1.…”

Section: Discussionmentioning

confidence: 99%

Low abundance of TFPI‐2 by both promoter methylation and miR‐27a‐3p regulation is linked with poor clinical outcome in gastric cancer

Geng

Liu

et al. 2020

The Journal of Gene Medicine

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Background:The tumor suppressor role of tissue factor pathway inhibitor 2 (TFPI-2) has been reported in various tumors. The present study aimed to improve the understanding of the oncogenic properties of TFPI-2 in gastric cancer. Methods:Relative expression of TFPI-2 was determined by a real-time polymerase chain reaction (PCR) and western blotting, respectively. Cell viability was measured via a cell counting kit-8 assay and proliferation was evaluated by a colony formation assay. Cell apoptosis was assessed with a caspase-3 activity kit and invasion was evaluated by a transwell chamber assay. The methylation level of TFPI-2 promoter was assayed by methylation-specific PCR. The regulatory effect of miR-27a-3p on TFPI-2 was analyzed with a luciferase reporter assay. The direct association between miR-27a-3p and TFPI-2 was shown by biotin-labelling pulldown.Results: TFPI-2 was down-regulated in gastric cancer, which associated with an unfavorable prognosis clinically. Ectopic introduction of TFPI-2 greatly compromised cell viability, colony formation and invasive capacity, and also induced cell apoptosis simultaneously. The promoter region of TFPI-2 was extensively methylated in gastric cancer tissues compared to normal tissues, suggesting the epigenetic inhibition of TFPI-2 expression. We further identified that TFPI-2 functioned as sponge RNA against miR-27a-3p. Most importantly, miR-27a-3p-specific inhibitor significantly exerted a tumor suppressor function akin to TFPI-2 itself, and the anti-tumoral activities were completely abolished by TFPI-2 knockdown. Conclusions:We found that the epigenetically suppressed TFPI-2 compromised sponging effects with respect to miR-27a-3p in gastric cancer, which consequently and mechanistically contributed to the tumor biology of gastric cancer. K E Y W O R D Sgastric cancer, methylation, miR-27a-3p, TFPI-2 Geng and Liu contributed equally to this work.

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“…The role of miR-27a in OC has also been reported. For instance, miR-27a promotes epithelial-mesenchymal transition (EMT) in OC by regulating FOXO1 expression [10]. MiR-27a also regulates the chemosensitivity of human OC cell lines by targeting Cullin 5 [11].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-induced up-regulation of miR-27a promotes paclitaxel resistance in ovarian cancer

et al. 2020

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Correspondence: Youguo Chen (youguo chen@163.com)Ovarian cancer (OC) is a malignant tumor with high mortality in women. Although cancer patients initially respond to paclitaxel chemotherapy following surgery, most patients will relapse after 12-24 months and gradually die from chemotherapy resistance. In OC, cancer cells become resistant to paclitaxel chemotherapy under hypoxic environment. The miR-27a has been identified as an oncogenic molecular in ovarian cancer, prostate cancer, liver cancer etc. In addition, the miR-27a is involved in hypoxia-induced chemoresistance in various cancers. However, the role of miR-27a in hypoxia-induced OC resistance remains unclear. The aim of the present study was to investigate the regulatory mechanism of miR-27a in hypoxia-induced OC resistance. The expression of HIF-1α induced Hypoxia overtly up-regulated. At the same time, hypoxia increased viability of Skov3 cells and decreased cell apoptosis when treated with paclitaxel. The expression of the miR-27a was obviously up-regulated under hypoxia and involved in hypoxia-induced paclitaxel resistance. Follow-up experiments portray that miR-27a improved paclitaxel resistance by restraining the expression of APAF1 in OC. Finally, we further elucidated the important regulatory role of the miR-27a-APAF1 axis in OC through in vivo experiments. According to our knowledge, we first reported the regulation of miR-27a in hypoxia-induced chemoresistance in OC, providing a possible target for chemoresistance treatment of OC.

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MiR-27a promotes EMT in ovarian cancer through active Wnt/𝜷-catenin signalling by targeting FOXO1

Cited by 52 publications

References 38 publications

Astragalus polysaccharides inhibit ovarian cancer cell growth via microRNA-27a/FBXW7 signaling pathway

Astragalus polysaccharides inhibit ovarian cancer cell growth via microRNA-27a/FBXW7 signaling pathway

Low abundance of TFPI‐2 by both promoter methylation and miR‐27a‐3p regulation is linked with poor clinical outcome in gastric cancer

Hypoxia-induced up-regulation of miR-27a promotes paclitaxel resistance in ovarian cancer

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