CircPVT1 promotes proliferation of lung squamous cell carcinoma by binding to miR-30d/e

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.

CircPVT1: a pivotal circular node intersecting Long Non-Coding-PVT1 and c-MYC oncogenic signals

“…Recent study of Huang M. and colleagues showed that circPVT1 is upregulated in cell upon irradiation treatment highlighting that silencing of circPVT1 enhances NSCLC cell sensitivity response by acting as a sponge for miRNA-1208 [ 96 ]. Recent study of Shi J. and colleagues, demonstrated that circPVT1 promotes the tumorigenic phenotype in lung squamous cell carcinoma by sequestering miR-30d and miR-30e thus upregulating their target CCNF (Chromatin Condensation and Nuclear Fragmentation), the substrate recognition subunit of SCF ubiquitin ligase complexes which has a pivotal role in cancer since it is able to sustain cell proliferation [ 61 ]. Another study of Danac J. M. C. and colleagues showed that circPVT1 upregulates NRAS (Neuroblastoma RAS viral oncogene homolog) by acting as a miRNA sponge on let-7 thus sustaining the oncogenic phenotype [ 62 ].…”

lncRNA PVT1: a novel oncogene in multiple cancers

“…Finally, Shi et al. [ 237 ] revealed that circPVT1 was significantly upregulated in the tissues, serum, and cell lines of patients with LSCC and promoted LSCC progression by increasing cyclin F expression, acting as a sponge for miR-30d and miR-30e.…”

Role of circular RNAs in the diagnosis, regulation of drug resistance and prognosis of lung cancer (Review)

“…Most available literature regarding research on circRNAs and lung cancer seems to be from studies published in Asia. To avoid differences between races, the present review uniformly selected studies with Asian patients (23,39,62,83,85,87,(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103)(104)(105)(106). Almost all circRNAs and tumor prognoses were associated with TNM stage and lymph node metastasis in the 20 groups of circRNAs listed in the table.…”

“…In the 40th month, the survival rate of the high expression group was only 50%, while the low expression group had a higher rate of ~90%. Shi et al ( 84 ) reported that patients with lung squamous cell carcinoma (LUSC) who expressed high levels of circ_PVT1 had a lower overall survival (OS) than patients with LUSC who expressed low levels of circ_PVT1. Multivariate analysis confirmed that circ_PVT1 expression is a potential independent predictor of OS.…”