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

Abstract

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 nonsmall 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 cancerpromoting 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.

Circular RNAs and Hepatocellular Carcinoma: New Epigenetic Players With Diagnostic and Prognostic Roles

“…Recent emerging evidence has demonstrated that circRNAs are closely associated with tumor initiation and progression (17)(18)(19)(20). Firstly, deregulation of circRNAs has been confirmed in many types of cancers, including breast cancer (21,22), lung cancer (23,24), prostate cancer (25), colorectal cancer (26), gastrointestinal cancers (27), ovarian cancer (28), thyroid cancer (29), gynecologic cancers (30), and hepatocellular carcinoma (31); Secondly, some circRNAs have been demonstrated to play either oncogenic (32,33) or tumor suppressive (34,35) roles in affecting multiple cancer hallmarks, including deregulating cellular energetic, self-sufficiency in growth signals, insensitivity anti-growth signals, evading cell death, limitless replicative potential, substained angiogenesis, tissue invasion and metastasis (36,37). Moreover, given the facts that circRNAs are more resistant to exoribonuclease degradation due to their lack of free 5′-and 3′-ends (38) and are abundant in body fluids, such as saliva, blood, and urine (39-41), they have been increasingly recognized as promising tumor biomarkers (42).…”

Hsa_circ_0001073 targets miR‐626/LIFR axis to inhibit lung cancer progression

“…The circRNA/microRNA (miRNA)/messenger RNA (mRNA) network is an important pathway for circRNA in regulating lung cancer progression 8 . Previous studies have reported that many circRNAs (like circ_0000284 and circ_0072088) can promote lung cancer development via regulating different miRNAs 9,10 . In this research, we aim to explore a new circRNA that is related to lung cancer progression.…”

A novel circular RNA hsa_circRNA_103809/miR-377-3p/GOT1 pathway regulates cisplatin-resistance in non-small cell lung cancer (NSCLC)

“…Consistently, Ling Liu et al reported that miR-377-3p was downregulated in cisplatinresistant osteosarcoma cells and tissues [24], which enlightened us to choose miR-377-3p for further investigations. In addition, miR-377-3p functioned as a tumor suppressor to hamper the development of multiple cancers, such as breast cancer [25], gastric cancer [26], ovarian cancer [27] and NSCLC [28][29][30]. Interestingly, miR-377-3p regulated drug resistance in cancer treatment, and Ling Liu et al reported that miR-377-3p participated in the regulation of cisplatinresistance in osteosarcoma [24], but the role of miR-377-3p in regulating cisplatin-sensitivity in NSCLC is still unknown.…”