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Hsa_circ_CSPP1/MiR-361-5p/ITGB1 Regulates Proliferation and Migration of Cervical Cancer (CC) by Modulating the PI3K-Akt Signaling Pathway

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Abstract

This study aimed to investigate the regulatory mechanism of circular RNA CSPP1 (hsa_circ_CSPP1) in cervical cancer. Based on GEO database, differentially expressed circRNAs and mRNAs related to cervical cancer were screened out by R software. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) term analysis were performed to analyze the functional and pathway enrichment of identified DEGs. In addition, Cytoscape software was used to build interaction network of DEGs. The mRNA expressions were examined by qRT-PCR. Western blot was conducted to view the expression of proteins. Cell proliferation and apoptosis were respectively evaluated using CCK-8 assay and flow cytometry, whereas cell migration abilities were detected by Transwell assay. The relationship among factors was validated by dual-luciferase reporter gene assay. The influence in cervical tumor growth was further verified through nude mouse model in vivo. Hsa_circ_CSPP1 and ITGB1 were high-expressed in cervical cancer, while miR-361-5p was low-expressed. Hsa_circ_CSPP1 knockdown or miR-361-5p overexpression could suppress cervical cancer cell proliferation and migration, whereas promoted cell apoptosis. In addition, further experiments demonstrated that both hsa_circ_CSPP1 and ITGB1 mRNA were targets of miR-361-5p. Repressing hsa_circ_CSPP1 restrained cell viability and mobility and induced apoptosis through sponging miR-361-5p. Meanwhile, miR-361-5p also inhibited cervical cancer tumorigenesis via downregulation of ITGB1. Knockdown of hsa_circ_CSPP1 impeded tumor growth through suppressing the expression of downstream gene ITGB1, PI3K, and Akt. Circular RNA hsa_circ_CSPP1 regulates cell migration and proliferation in cervical cancer through miR-361-5p/ITGB1 in PI3K-Akt signaling pathway.

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References

  1. Forouzanfar MH, Foreman KJ, Delossantos AM, Lozano R, Lopez AD, Murray CJ, et al. Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. Lancet. 2011;378:1461–84.

    Article  Google Scholar 

  2. Teng P, Jiao Y, Hao M, Tang X. MicroRNA-383 suppresses the PI3K-AKT-MTOR signaling pathway to inhibit development of cervical cancer via down-regulating PARP2. J Cell Biochem. 2018;119:5243–52.

    Article  CAS  Google Scholar 

  3. Zhang J, Zhao X, Zhang J, Zheng X, Li F. Circular RNA hsa_circ_0023404 exerts an oncogenic role in cervical cancer through regulating miR-136/TFCP2/YAP pathway. Biochem Biophys Res Commun. 2018;501:428–33.

    Article  CAS  Google Scholar 

  4. Li P, Chen S, Chen H, et al. Using circular RNA as a novel type of biomarker in the screening of gastric cancer. Clin Chim Acta. 2015;444:132–6.

    Article  CAS  Google Scholar 

  5. Santos JMO, Peixoto da Silva S, Costa NR, Gil da Costa RM, Medeiros R. The role of microRNAs in the metastatic process of high-risk HPV-induced cancers. Cancers (Basel). 2018;10.

  6. Zhang H, Zhang Z, Wang S, Zhang S, Bi J. The mechanisms involved in miR-9 regulated apoptosis in cervical cancer by targeting FOXO3. Biomed Pharmacother. 2018;102:626–32.

    Article  CAS  Google Scholar 

  7. Wang X, Tang S, Le SY, et al. Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One. 2008;3:e2557.

    Article  Google Scholar 

  8. Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006;9:189–98.

    Article  CAS  Google Scholar 

  9. Xu J, Li Y, Wang F, Wang X, Cheng B, Ye F, et al. Suppressed miR-424 expression via upregulation of target gene Chk1 contributes to the progression of cervical cancer. Oncogene. 2013;32:976–87.

    Article  CAS  Google Scholar 

  10. Wu X, Xi X, Yan Q, et al. MicroRNA-361-5p facilitates cervical cancer progression through mediation of epithelial-to-mesenchymal transition. Med Oncol. 2013;30:751.

    Article  Google Scholar 

  11. Liu S, Song L, Yao H, et al. Preserved miR-361-3p expression is an independent prognostic indicator of favorable survival in cervical cancer. Dis Markers. 2018;2018:8949606.

    PubMed  PubMed Central  Google Scholar 

  12. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495:384–8.

    Article  CAS  Google Scholar 

  13. Giancotti FG. Deregulation of cell signaling in cancer. FEBS Lett. 2014;588:2558–70.

    Article  CAS  Google Scholar 

  14. Liu QZ, Gao XH, Chang WJ, Gong HF, Fu CG, Zhang W, et al. Expression of ITGB1 predicts prognosis in colorectal cancer: a large prospective study based on tissue microarray. Int J Clin Exp Pathol. 2015;8:12802–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Perez-Ramirez C, Canadas-Garre M, Molina MA, Faus-Dader MJ, Calleja-Hernandez MA. PTEN and PI3K/AKT in non-small-cell lung cancer. Pharmacogenomics. 2015;16:1843–62.

    Article  CAS  Google Scholar 

  16. Martini M, De Santis MC, Braccini L, Gulluni F, Hirsch E. PI3K/AKT signaling pathway and cancer: an updated review. Ann Med. 2014;46:372–83.

    Article  CAS  Google Scholar 

  17. Ma YY, Wei SJ, Lin YC, Lung JC, Chang TC, Whang-Peng J, et al. PIK3CA as an oncogene in cervical cancer. Oncogene. 2000;19:2739–44.

    Article  CAS  Google Scholar 

  18. Matsuoka T, Yashiro M, Nishioka N, Hirakawa K, Olden K, Roberts JD. PI3K/Akt signalling is required for the attachment and spreading, and growth in vivo of metastatic scirrhous gastric carcinoma. Br J Cancer. 2012;106:1535–42.

    Article  CAS  Google Scholar 

  19. Tian L, Zhao Z, Xie L, Zhu J. MiR-361-5p suppresses chemoresistance of gastric cancer cells by targeting FOXM1 via the PI3K/Akt/mTOR pathway. Oncotarget. 2018;9:4886–96.

    PubMed  Google Scholar 

  20. Dong Y, He D, Peng Z, et al. Circular RNAs in cancer: an emerging key player. J Hematol Oncol. 2017;10:2.

    Article  Google Scholar 

  21. Sand M, Bechara FG, Gambichler T, Sand D, Bromba M, Hahn SA, et al. Circular RNA expression in cutaneous squamous cell carcinoma. J Dermatol Sci. 2016;83:210–8.

    Article  CAS  Google Scholar 

  22. Wang H, Zhao Y, Chen M, Cui J. Identification of novel long non-coding and circular RNAs in human papillomavirus-mediated cervical cancer. Front Microbiol. 2017;8:1720.

    Article  Google Scholar 

  23. Gao YL, Zhang MY, Xu B, et al. Circular RNA expression profiles reveal that hsa_circ_0018289 is up-regulated in cervical cancer and promotes the tumorigenesis. Oncotarget. 2017;8:86625–33.

    PubMed  PubMed Central  Google Scholar 

  24. Xu Z, Zou L, Ma G, Wu X, Huang F, Feng T, et al. Integrin beta1 is a critical effector in promoting metastasis and chemo-resistance of esophageal squamous cell carcinoma. Am J Cancer Res. 2017;7:531–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Meenakshi Sundaram DN, Kucharski C, Parmar MB, Kc RB, Uludag H. Polymeric delivery of siRNA against integrin-beta1 (CD29) to reduce attachment and migration of breast cancer cells. Macromol Biosci. 2017;17.

    Article  Google Scholar 

  26. Lau MT, So WK, Leung PC. Integrin beta1 mediates epithelial growth factor-induced invasion in human ovarian cancer cells. Cancer Lett. 2012;320:198–204.

    Article  CAS  Google Scholar 

  27. Hazlehurst LA, Argilagos RF, Dalton WS. Beta1 integrin mediated adhesion increases Bim protein degradation and contributes to drug resistance in leukaemia cells. Br J Haematol. 2007;136:269–75.

    Article  CAS  Google Scholar 

  28. Zhan P, Liu L, Liu B, Mao XG. Expression of integrin beta1 and its significance in squamous cell carcinoma of the cervix. Mol Med Rep. 2014;9:2473–8.

    Article  CAS  Google Scholar 

  29. Zhang W, Zhang M, Liu L, et al. MicroRNA-183-5p inhibits aggressiveness of cervical cancer cells by targeting integrin subunit beta 1 (ITGB1). Med Sci Monit. 2018;24:7137–45.

    Article  CAS  Google Scholar 

  30. Lu L, Sun J, Shi P, et al. Identification of circular RNAs as a promising new class of diagnostic biomarkers for human breast cancer. Oncotarget. 2017;8:44096–107.

    PubMed  PubMed Central  Google Scholar 

  31. Fadejeva I, Olschewski H, Hrzenjak A. MicroRNAs as regulators of cisplatin-resistance in non-small cell lung carcinomas. Oncotarget. 2017;8:115754–73.

    Article  Google Scholar 

  32. Li F, Zhang L, Li W, Deng J, Zheng J, An M, et al. Circular RNA ITCH has inhibitory effect on ESCC by suppressing the Wnt/beta-catenin pathway. Oncotarget. 2015;6:6001–13.

    PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Gynecology, Jiangxi Maternal and Child Health Hospital, 318 Bayi Road, Donghu, Nanchang, 330006, Jiangxi, People’s Republic of China

    Wenjie Yang

  2. Center of Health Management Physical Examination, Jiangxi Maternal and Child Health Hospital, 318 Bayi Road, Donghu, Nanchang, 330006, Jiangxi, People’s Republic of China

    Tong Xie

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  1. Wenjie Yang
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Contributions

Substantial contribution to the conception and design of the work: Wenjie Yang and Tong Xie; Analysis and interpretation of the data: Tong Xie; Drafting the manuscript: Wenjie Yang; Revising the work critically for important intellectual content: Wenjie Yang; Final approval of the work: All authors.

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Correspondence to Wenjie Yang.

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This study was authorized by Jiangxi Maternal and Child Health Hospital and obtained written informed consents from all the participants.

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Yang, W., Xie, T. Hsa_circ_CSPP1/MiR-361-5p/ITGB1 Regulates Proliferation and Migration of Cervical Cancer (CC) by Modulating the PI3K-Akt Signaling Pathway. Reprod. Sci. 27, 132–144 (2020). https://doi.org/10.1007/s43032-019-00008-5

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  • DOI: https://doi.org/10.1007/s43032-019-00008-5

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