<p>CircSEC31A Promotes the Malignant Progression of Non-Small Cell Lung Cancer Through Regulating SEC31A Expression via Sponging miR-376a</p>

Abstract

Background Circular RNAs (circRNAs) have recently been shown as important regulators in the pathogenesis of non-small cell lung cancer (NSCLC). The purpose of this work was to explore the precise parts played by circRNA SEC31 homolog A (circSEC31A, hsa_circ_0001421) in NSCLC malignant progression. Methods The expression levels of circSEC31A, miR-376a and SEC31 homolog A (SEC31A) were gauged by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. Subcellular fractionation assay was used to determine the subcellular localization of circSEC31A, and RNase R assay was performed to assess the stability of circSEC31A. Cell migration and invasion were detected by transwell assay, and cell apoptosis was evaluated using flow cytometry. Measurement of glucose consumption, lactate production and adenosine triphosphate (ATP) level were done using corresponding assay kits. The targeted interactions among circSEC31A, miR-376a and SEC31A were confirmed by the dual-luciferase reporter and RNA pull-down assays. Animal studies were performed to observe the role of circSEC31A in tumor growth in vivo. Results Our data indicated that circSEC31A and SEC31A were upregulated in NSCLC tissues and cells. CircSEC31A knockdown suppressed NSCLC cell migration, invasion, glycolysis and promoted apoptosis in vitro, as well as hindered tumor growth in vivo. Mechanistically, circSEC31A directly interacted with miR-376a, and circSEC31A depletion regulated NSCLC cell malignant progression by miR-376a. Moreover, SEC31A was a functional target of miR-376a, and it mediated the regulatory impact of miR-376a overexpression on NSCLC cell progression. Furthermore, circSEC31A controlled SEC31A expression through acting as a miR-376a sponge. Conclusion Our findings first identified that the knockdown of circSEC31A suppressed NSCLC malignant progression at least partly through modulating SEC31A expression by acting as a miR-376a sponge, providing a novel molecular target of NSCLC therapy.

Circular RNA circ_0003028 contributes to tumorigenesis by regulating GOT2 via miR-1298-5p in non-small cell lung cancer

“…For example, Li et al displayed that the forced expression of hsa_-circ_0046263 could aggravate the malignancy of the tumor by boosting carcinogenesis and metastasis in NSCLC cells [11]. Analogously, Cheng et al presented that the reduced expression of circSEC31A could repress cell migration, invasion, and glycolysis through binding to miR-376a in NSCLC cells [12]. Notably, prior research described that circ_0003028, a novel circRNA originating from Fucosyltransferase 8 (FUT8), has been proven to be increased in liver cancer for the first time [13].…”

Circ_0078767 Inhibits the Progression of Non-Small-Cell Lung Cancer by Regulating the GPX3 Expression by Adsorbing miR-665

“…The role of circRNAs in regulating glycolysis in cancer disease has been extensively studied in recent years [ 33 ]. For example, downregulation of circSEC31A or circ_0000735 can inhibit glycolytic metabolism in NSCLC cells [ 34 , 35 ]. In this study, knocking down circ_0078767 significantly promoted the proliferation, migration, and invasion of NSCLC cells.…”

Biogenesis, Functions, and Role of CircRNAs in Lung Cancer

“…CircSEC31A and SEC31A were significantly highly expressed in NSCLC cells and tissues, and circSEC31A expression levels were closely associated with tumor size, TNM stage, and lymphatic metastasis. 57 CircSEC31A could promote NSCLC cell migration, invasion, glycolysis, and apoptosis by sponging miR-376a, and SEC31A was directly targeted and inhibited by miR-376a in NSCLC Cells. That is to say, circSEC31A promoted NSCLC malignant progression through modulating SEC31A expression by acting as a miR-376a sponge.…”