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CircRNA hsa_circ_0002577 accelerates endometrial cancer progression through activating IGF1R/PI3K/Akt pathway.

ABSTRACT: BACKGROUND:Endometrial cancer (EC) is a common gynecologic malignancy worldwide. This study investigated the regulatory effects of circular RNA (circRNA) hsa_circ_0002577 on the tumorigenesis of EC. METHODS:Tumor samples and adjacent normal tissues were obtained from 84 EC patients. Recombinant lentiviral vectors expressing hsa_circ_0002577 (Lv-circRNA), short hairpin RNAs against hsa_circ_0002577 (sh-circRNA), miR-625-5p mimics, miR-625-5p inhibitor, lentiviral vectors expressing insulin-like growth factor 1 receptor (IGF1R) and their corresponding controls were transfected into EC cells as designated. A mouse xenograft model was established in BALB/c mice by inoculating Ishikawa cells transfected with sh-circRNA or control sequence. RESULTS:Hsa_circ_0002577 was upregulated in EC tissue samples and cells as compared to normal controls. EC patients with higher expression of hsa_circ_0002577 showed poorer overall survival and more advanced tumor stage. EC cells transfected with Lv-circRNA showed promoted proliferation, migration, and invasion, whereas the delivery of sh-circRNA exerted an opposite effect. Further analyses showed that hsa_circ_0002577 acted as a miR-625-5p sponge in EC cells. IGF1R was a potential downstream target of miR-625-5p. The expression of IGF1R in EC tissues was significantly higher than that in matched controls. Hsa_circ_0002577 accelerated EC development by inducing IGF1R expression and activating PI3K/Akt signaling pathway. Also, the knockdown of hsa_circ_0002577 delayed tumor growth and metastasis in the inoculated mice. CONCLUSION:Our study showed that circRNA hsa_circ_002577 accelerated EC progression by acting as a miR-625-5p sponge, upregulating IGF1R and activating the PI3K/Akt pathway, suggesting the potential therapeutic use of hsa_circ_002577 in EC treatment. TRIAL REGISTRATION:Not Applicable.

SUBMITTER: Wang Y

PROVIDER: S-EPMC7450704 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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CircRNA hsa_circ_0002577 accelerates endometrial cancer progression through activating IGF1R/PI3K/Akt pathway.

Wang Yu Y Yin Lili L Sun Xiaofei X

Journal of experimental & clinical cancer research : CR 20200826 1

<h4>Background</h4>Endometrial cancer (EC) is a common gynecologic malignancy worldwide. This study investigated the regulatory effects of circular RNA (circRNA) hsa_circ_0002577 on the tumorigenesis of EC.<h4>Methods</h4>Tumor samples and adjacent normal tissues were obtained from 84 EC patients. Recombinant lentiviral vectors expressing hsa_circ_0002577 (Lv-circRNA), short hairpin RNAs against hsa_circ_0002577 (sh-circRNA), miR-625-5p mimics, miR-625-5p inhibitor, lentiviral vectors expressing ...[more]

PMID: 32847606

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Project description:BackgroundIncreasing studies have revealed that circular RNAs (CircRNAs) make great contributions to regulating tumor progression. Therefore, we intended to explore the expression characteristics, function, and related mechanisms of a novel type of circRNA, PIP5K1A, in glioma.MethodsFirstly, reverse transcription-polymerase chain reaction (RT-PCR) was carried out to examine CircPIP5K1A expression in glioma tissues and adjacent normal tissues, and the correlation between CircPIP5K1A level and the clinical-pathological indicators of glioma was analyzed. Then, the CircPIP5K1A expression in various glioma cell lines was detected, and CircPIP5K1A overexpression and knockdown cell models were constructed. Subsequently, cell proliferation and viability were detected by the CCK8 method and BrdU staining. Cell apoptosis was detected by flow cytometry, and cell invasion was examined by Transwell assay. The expression of TCF12, PI3K/AKT pathway apoptotic related proteins (Caspase3, Bax, and Bcl2) and epithelial-mesenchymal transition (EMT) markers (E-cadherin, Vimentin, and N-cadherin) was determined by western blot or RT-PCR.ResultsThe results manifested that CircPIP5K1A was upregulated in glioma tissues (compared with that in normal adjacent tissues), and overexpressed CircPIP5K1A was related to glioma volume and histopathological grade. Functionally, overexpressing CircPIP5K1A notably elevated glioma cell proliferation, invasion, and EMT and inhibited apoptosis both in vivo and in vitro. Besides, CircPIP5K1A upregulated TCF12 and PI3K/AKT activation. Bioinformatics analysis testified that miR-515-5p was a common target of CircPIP5K1A and TCF12, while the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) experiment further confirmed that CircPIP5K1A targeted miR-515-5p, which bound the 3'-untranslated region (UTR) of TCF12.ConclusionsOverall, the study illustrated that CircPIP5K1A is a potential prognostic marker in glioma and regulates glioma evolvement by modulating the miR-515-5p-mediated TCF12/PI3K/AKT axis.

Dataset Information

CircRNA hsa_circ_0002577 accelerates endometrial cancer progression through activating IGF1R/PI3K/Akt pathway.

Publications

CircRNA hsa_circ_0002577 accelerates endometrial cancer progression through activating IGF1R/PI3K/Akt pathway.

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