Abstract
BackgroundNon-small cell lung cancer (NSCLC) is a threat to human health. Circular RNAs (circRNAs) have been proved to function in NSCLC development. In this study, the role of circRNA hsa_circ_0010235 in NSCLC progression and the possible molecular mechanism were explored.MethodsExpression of hsa_circ_0010235, miRNA (miR)-433-3p and TOR signaling pathway regulator-like (TIPRL) was examined by quantitative real-time PCR (qRT-PCR). Cell viability and clonogenicity were detected by cell counting kit-8 (CCK-8) assay and colony formation assay, respectively. Flow cytometry was performed to monitor cell apoptosis and cell cycle distribution. Western blot assay was employed to evaluate the protein levels of TIPRL, light chain 3 (LC3)-II/I and p62. Cell metastasis was assessed by Transwell and wound healing assays. The targeted relationship between miR-433-3p and hsa_circ_0010235 or TIPRL was confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Furthermore, the role of hsa_circ_0010235 in vivo was investigated by xenograft assay.ResultsHsa_circ_0010235 and TIPRL were highly expressed in NSCLC tissues and cells, while miR-433-3p was downregulated. Depletion of hsa_circ_0010235 or gain of miR-433-3p repressed proliferation and autophagy but promoted apoptosis in NSCLC cells. Hsa_circ_0010235 sponged miR-433-3p to upregulate TIPRL expression, so as to affect NSCLC development. Hsa_circ_0010235 knockdown also blocked tumor growth in vivo.ConclusionHsa_circ_0010235 knockdown suppressed NSCLC progression by regulating miR-433-3p/TIPRL axis, affording a novel mechanism of NSCLC progression.
Highlights
Non-small cell lung cancer (NSCLC) is a threat to human health
Hsa_circ_0010235 was highly expressed in NSCLC tissues and cells At first, the expression level of hsa_circ_0010235 in NSCLC tissues was evaluated by quantitative real-time PCR (qRT-PCR) assay
Follow-up results of these 52 patients revealed that NSCLC patients with higher hsa_circ_0010235 expression had lower overall survival rate
Summary
Non-small cell lung cancer (NSCLC) is a threat to human health. Circular RNAs (circRNAs) have been proved to function in NSCLC development. The role of circRNA hsa_circ_0010235 in NSCLC progression and the possible molecular mechanism were explored. Lung cancer is one of the most commonly diagnosed malignancies all over the world, with high mortality [1]. Non-small cell lung cancer (NSCLC) is the main subtype of lung cancers, composing ~ 85% of all lung tumors [2]. Due to lacking symptoms at early stages in most NSCLC patients, as well as the high rates of metastasis and relapse, the 5-year survival rate of NSCLC patients is Circular RNAs (circRNAs) are a class of non-coding RNA molecules, characterized by the special closed-loop structure, making them resistant to RNase R (an exoribonuclease) [4]. Back-spliced from aldehyde dehydrogenase 4 family member A1 (ALDH4A1), Zhang et al Cancer Cell Int (2021) 21:73
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