Red de regulación hsa_circ_0009910/miR-198/c-MET: posible papel en la carcinogénesis cervical.

Abstract

Background: Circular RNAs (circRNAs) are a type of non-coding RNA recently identified as regulators of tumorigenesis due they are efficient competing endogenous RNAs (ceRNAs) and regulate important processes such as transcription, proliferation, invasion, among others. However, the expression profiles, and possible roles of hsa_circ_0008563 and hsa_circ_0009910 in cervical cancer are unknown. Objective: Identify differentially expressed circRNAs (DECs), perform circRNAs-miRNAs-mRNAs regulatory networks, and evaluate their role in regulating mRNA expression in HeLa cells. Material and methods: Bioinformatic analysis was performed using the Gene Expression Omnibus (GEO) repository to identify DECs in HeLa cells. Selected candidates were validated by RT-qPCR. In addition, a circRNA-miRNA-mRNA regulatory network was established and Gene Ontology (GO) of the mRNAs of each network was subsequently performed. Knockdown of hsa_circ_0009910 was made by transfecting interference RNAs and the mRNA levels of c-MET was evaluated by RT-qPCR. Results: 25 DECs were identified in HeLa cells, of which hsa_circ_0008563 and hsa_circ_0009910 were overexpressed in HeLa cells. The interaction network revealed that hsa_circ_0008563 can regulate four miRNAs, three proteins and 92 mRNAs (indirectly to mRNAs); while hsa_circ_0009910 can regulate ten miRNAs, seven proteins and 135 mRNAs. GO analysis suggested that the 135 mRNAs of hsa_circ_0009910 network are involved in processes such as apoptosis, cell adhesion, cell proliferation and other important biological processes in cancer development. Likewise, the GO of the mRNAs regulated by hsa-miR-198 participate in processes such as proliferation, cell cycle, cell death and other biological processes. Furthermore, hsa_circ_0009910 knockdown showed a decrease in c-MET expression in HeLa cells. Conclusion: Overexpression of hsa_circ_0009910 promotes cervical carcinogenesis by of overexpression of the c-MET oncogene, possibly through its function as a ceRNA.