Circ_0003028 enhances the proliferation and glycolytic capacity and suppresses apoptosis in non-small cell lung cancer cells via the miR-1305/miR-1322-SLC5A1 axis

Abstract

Background Circular RNA (circRNA), a unique RNA molecule with a circular structure, is relevant to the process of non-small cell lung cancer (NSCLC). However, the role and possible mechanisms of circ_0003028 in NSCLC are not completely clear. Here, we investigated the role of circ_0003028 in NSCLC progression. Methods We first confirmed the stability and head-to-tail junction sequences of circ_000302. Circ_0003028 expression was identified with quantitative reverse transcription polymerase chain reaction (qRT-PCR) in NSCLC tissues, and the survival probability and prognosis were analyzed using Kaplan-Meier survival and receiver operating characteristic (ROC) analyses. Functionally, the proliferation, apoptosis, and glycolytic capacity were examined using cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) staining, a flow cytometer, commercial kits [glucose, lactate, and adenosine triphosphate (ATP)], and a Seahorse XF extracellular flux analyzer. Moreover, the potential microRNAs (miRNAs) of circ_0003028 were predicted and identified, and the target gene of miRNA (miR)-1322 and miR-1305 were also screened using DIANA-microT and TargetScan. Results We first determined the head-to-tail junction sequences of circ_0003028 and its stability. Circ_0003028 was also confirmed to be upregulated in NSCLC tissues. Meanwhile, circ_0003028 had poor overall survival and high diagnostic potential in NSCLC patients. Furthermore, we found that overexpression of circ_0003028 could increase the proliferation and glycolytic capacity and restrain the apoptosis of NSCLC cells, and circ_0003028 silencing played the opposite role to circ_0003028 overexpression. Moreover, circ_0003028 might regulate miR-1305 and miR-1322, which might further regulate solute carrier family 5 member 1 (SLC5A1). Conclusions Circ_0003028 could accelerate the malignant behaviors and glycolytic capacity of NSCLC cells via a mechanism that may be related to miR-1305 or the miR-1322/SLC5A1 axis. Therefore, the findings of the current study provide a preliminary theoretical basis for NSCLC therapy and diagnosis.