Abstract
Background: Circular RNAs (circRNAs) are a new type of extensive non-coding RNAs that regulate the activation and progression of different human diseases, including cancer. However, information on the underlying mechanisms and clinical significance of circRNAs in lung squamous cell carcinoma (LUSC) remains scant. Methods: The expression profile of RNAs in 8 LUSC tissues, and 9 healthy lung tissues were assayed using RNA sequencing (RNA-seq) techniques. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to profile the expression of circPVT1 and its relationship with the prognosis of LUSC, i.e., survival analysis. Moreover, in vitro and in vivo experiments were performed to evaluate the impacts of circPVT1 on the growth of tumors. RNA pull-down tests, mass spectrometry, dual-luciferase reporter assessment, and RNA immune-precipitation tests were further conducted to interrogate the cross-talk between circPVT1, HuR, or miR-30d/e in LUSC. Results: Our data showed that circPVT1 was upregulated in LUSC tissues, serum, and cell lines. LUSC patients with higher circPVT1 expression exhibited shorter survival rates. The in vivo and in vitro data revealed that circPVT1 promotes the proliferation of LUSC cells. Additionally, mechanistic analysis showed that HuR regulated circPVT1. On the other hand, circPVT1 acted as a competing endogenous RNA (ceRNA) of miR-30d and miR-30e in alleviating the suppressive influences of miR-30d and miR-30e on its target cyclin F (CCNF). Conclusion: CircPVT1 promotes LUSC progression via HuR/circPVT1/miR-30d and miR-30e/CCNF cascade. Also, it acts as a novel diagnostic biomarker or treatment target of individuals diagnosed with LUSC.