Dataset Information

Circ_0039787 promotes cervical cancer cell tumorigenesis by regulation of the miR-877-5p-KRAS axis.

ABSTRACT: Circular RNA (circRNA) is a novel type of RNA that plays an important role in the occurrence and development of many malignant tumors. However, the potential regulatory role and molecular mechanisms of circRNAs in cervical cancer (CC) are still not clear. Here, we explored circRNAs associated with CC from the Gene Expression Omnibus (GEO) datasets GSE113696 and GSE102686. We initially identified circ_0039787, which is derived from exons 2 to 3 of the C16orf70 gene. We observed that circ_0039787 is mainly located in the cytoplasm and is more stable than its linear counterpart, C16orf70. circ_0039787 is significantly upregulated in CC tissues and cells. In addition, functional gain and loss experiments demonstrated that circ_0039787 promotes the proliferation, migration, and invasion of CC cells in vitro and the growth of CC tumors in vivo. Mechanistically, circ_0039787 promotes CC tumor progression by competitively absorbing miR-877-5p to alleviate the inhibitory effect of miR-877-5p on Kirsten Rat Sarcoma viral oncogene homolog (KRAS) expression. Overall, our results suggest that circ_0039787 could serve as a promising diagnostic biomarker and potential therapeutic target for CC patients.

SUBMITTER: He X

PROVIDER: S-EPMC10911348 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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circ_0039787 promotes cervical cancer cell tumorigenesis by regulation of the miR-877-5p-KRAS axis.

He Xiuchao X Sun Jing J Zhang Jing J Zhu Binbin B Jin Lufei L Wang Jianhua J Guan Qingyan Q

Aging 20240202 3

Circular RNA (circRNA) is a novel type of RNA that plays an important role in the occurrence and development of many malignant tumors. However, the potential regulatory role and molecular mechanisms of circRNAs in cervical cancer (CC) are still not clear. Here, we explored circRNAs associated with CC from the Gene Expression Omnibus (GEO) datasets GSE113696 and GSE102686. We initially identified circ_0039787, which is derived from exons 2 to 3 of the C16orf70 gene. We observed that circ_0039787 ...[more]

PMID: 38309290

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Project description:BackgroundCervical cancer is one of the most common malignancies in women, leading to major health problems for its high morbidity and mortality. Numerous studies have demonstrated that circular RNAs (circRNAs) could be participated in the progression of multifarious diseases, especially plentiful carcinomas. CircAMOTL1 (angiomotin-like1, ID: hsa_circ_0004214), which is located on human chromosome 11:9 4532555-94533477, is involved in the occurrence of breast cancer, etc. However, the intrinsic and concrete molecular mechanism of circAMOTL1 in cervical carcinomas remained thoroughly unclear, which was also the bottleneck of circRNAs studies in cancer.MethodsThe relative expression levels of circAMOTL1 and miR-526b in cervical carcinoma patients' specimens and cervical carcinoma cell lines were detected by RT-qPCR. Through experiments including loss-function and overexpression, the biological effects of circAMOTL1 and miR-526b on the proliferation, migration, apoptosis, and tumorigenicity were explored in cervical carcinomas. Dual luciferase reporter gene analysis, western blot, and other methods were adopted to explore the circAMOTL1 potential mechanism in cervical carcinomas.ResultsIn our experiments, our researches displayed that circAMOTL1 was significantly higher expression in cervical carcinomas specimens and cell lines. Further experiments illustrated that the knockdown of circAMOTL1 could restrain the malignant phenotype, AKT signaling, and epithelial-mesenchymal transition (EMT) of in cervical carcinomas cells. Meanwhile miR-526b was downregulated in cervical carcinomas and even miR-526b could partially reverse circAMOTL1 function in malignant cervical tumor cells. CircAMOTL1 acts as a microRNA (miRNA) sponge that actively regulates the expression of salt-inducible kinase 2 (SIK2) to sponge miR-526b and subsequently increases malignant phenotypes of cervical carcinomas cells. In a word, circAMOTL1 acts a carcinogenic role and miR-526b serves as the opposite function of antioncogene in the cervical carcinoma pathogenesis.ConclusionCircAMOTL1-miR-526b-SIK2 axis referred to the malignant progression and development of cervical carcinomas. CircAMOTL1 expression was inversely correlated with miR-526b and positively correlated with SIK2 mRNA in cervical cancer tissues. Thus, circAMOTL1 exerted an oncogenic role in cervical cancer progression through sponging miR-526b. Taken together, our study revealed that circAMOTL1 acted as an oncogene and probably was a potential therapeutic target for the cervical cancer.

Dataset Information

Circ_0039787 promotes cervical cancer cell tumorigenesis by regulation of the miR-877-5p-KRAS axis.

Publications

circ_0039787 promotes cervical cancer cell tumorigenesis by regulation of the miR-877-5p-KRAS axis.

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