circCD151 promotes GLI2 expression by regulating miR‑30d‑5p and enhancing proliferation, invasion and stemness of lung cancer

Abstract

To investigate the changes of circular (circ)rna circcd151 expression in lung cancer tissues and cells and its effects on proliferation, migration and invasion of lung cancer cells. The relative expression levels of circcd151 in lung cancer tissues and lung cancer cells (a549 and nci-H292) were determined by reverse transcription-quantitative Pcr. The effects of silencing or upregulation of circcd151 on the activity and clonal forming ability of a549 and nci-H292 cells were detected by ccK-8 and cloning formation experiments. Transwell invasion assay detected the effects of silencing or upregulation of circcd151 on the migration and invasion ability of a549 and nci-H292 cells. The regulatory effect of circcd151 on mir-30d-5p was detected by dual luciferase reporter gene. The relative expression level of circcd151 in lung cancer tissues was significantly higher compared with that in adjacent tissues. The relative expression level of circcd151 in A549 and NCI-H292 cells was significantly higher compared with that in human lung epithelial cells. in a549 and nci-H292 cells, silencing circcd151 decreased cell activity and clonal formation ability and invasion ability was also significantly decreased. circcd151 was upregulated in a549 and nci-H292 cells and the activity and clonal formation ability of a549 and NCI-H292 cells were significantly increased and the invasion ability was also significantly increased. double luciferase reporter assay confirmed the ceRNA regulatory mechanism of circcd151/mir-30d-5p/Gli2. in the present study, in vivo and in vitro functional studies demonstrated that circcd151 may promote the proliferation, invasion and cell stemness of lung cancer cells. Further molecular mechanism studies demonstrated that circcd151 could promote the malignant proliferation of lung adenocarcinoma by targeting mir-30d-5p and upregulating Gli2 expression. From the perspective of circrna, the present study will provide new clues to the pathogenesis and prognostic judgment of lung adenocarcinoma and provide a new target for clinical treatment.

miR-30d-5p: A Non-Coding RNA With Potential Diagnostic, Prognostic and Therapeutic Applications

“…In lung cancer, miR-30d-5p also had the function of reducing tumor occurrence and development, which depended on the ceRNA regulatory mechanism of circCD151/miR-30d-5p/GLI2 (Zhao et al, 2021). Taken together, researches into miR-30d-5p in tumorigenesis have progressed, while the specific mechanism needs further investigations.…”

“…By targeting CCNE2, miR-30d-5p was shown to have an anticancer role (Li et al, 2017;Hosseini et al, 2018). More importantly, since the expression level of miR-30d-5p in tumors clearly differed from that in surrounding tissues, the expression of miR-30d-5p in tumor tissue decreased significantly (Zhao et al, 2021). Therefore, it was considered as a possibly important factor connected with the clinical diagnosis and treatment of NSCLC (Zhang et al, 2017;Gao et al, 2018).…”

“…Therefore, it was considered as a possibly important factor connected with the clinical diagnosis and treatment of NSCLC (Zhang et al, 2017;Gao et al, 2018). Interestingly, the content of miR-30d-5p varied between different grades of NSCLC, indicating that miR-30d-5p was associated with the occurrence and progression of NSCLC (Xue et al, 2021;Zhao et al, 2021). In addition, Qi et al indicated that the expression of miR-30d-5p in LUSC cells was significantly downregulated, and the proliferation, migration and invasion of tumor cells were subsequently reduced, indicating that miR-30d-5p had a clear antitumor effect (Qi et al, 2021).…”

Tspan protein family: focusing on the occurrence, progression, and treatment of cancer

“…MicroRNAs can also serve as targets of Tspan genes or mRNAs. For instance, CircTspan24 targets miR-30d-5p to upregulate the expression of GLI2(Glioma cancer-related gene homologous protein 2) and promote the malignant proliferation of lung adenocarcinoma and promote the malignant proliferation of lung adenocarcinoma [ 135 ]. Increasing evidence suggests that there is aberrant expression of miR-203 in tumor stem cells, and it has been found that Tspan27 upregulates the expression of miR-203, which in turn regulates the expression of FZD2 [ 136 ].…”