Circular RNA circ_0000284 plays an oncogenic role in the progression of non-small cell lung cancer through the miR-377-3p-mediated PD-L1 promotion

Lung Cancer

Li L, et al. Cancer Cell Int 2020.


BACKGROUND: Circular RNAs (circRNAs), a subgroup of non-coding RNAs, are recognized as pivotal mediators in various types of cancers. CircRNA_0000284 (circ_0000284) was manifested to participate in the development of non-small cell lung cancer (NSCLC). The novel functional mechanism of circ_0000284 in NSCLC was investigated in our current study.

METHODS: We exploited quantitative real-time polymerase chain reaction (qRT-PCR) to analyze the relative RNA (circRNA, miRNA and mRNA) expression. The assessment of cell proliferation and colony formation was executed by Cell Counting Kit-8 (CCK-8) and colony formation assay, respectively. Transwell assay was implemented to examine cell migration and invasion. All protein levels were assayed using western blot. The role of circ_0000284 in vivo was evaluated via xenograft model. The target relation was estimated by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays.

RESULTS: As for the biological characterization, circ_0000284 was highly stable and localized in the cytoplasm. Circ_0000284 was up-regulated in NSCLC and could predict poor prognosis of NSCLC patients. Both in vitro and in vivo, down-regulation of circ_0000284 refrained tumorigenesis of NSCLC. Besides, microRNA-377-3p (miR-377-3p) was a miRNA target of circ_0000284, and targeted programmed death-ligand 1 (PD-L1). Circ_0000284 was a cancer-promoting circRNA in NSCLC via regulating the miR-377-3p/PD-L1 axis.

CONCLUSION: Thus, our results unraveled that circ_0000284 facilitated the progression of NSCLC by up-regulating the PD-L1 expression as a competing endogenous RNA (ceRNA) of miR-377, possibly developing a different perspective in understanding the molecular pathogenesis of NSCLC.