Downregulation of miR‐33b promotes non‐small cell lung cancer cell growth through reprogramming glucose metabolism miR‐33b regulates non‐small cell lung cancer cell growth

Abstract

Glucose metabolism is a common target for cancer regulation and microRNAs (miRNAs) are important regulators of this process. Here we aim to investigate a tumor‐suppressing miRNA, miR‐33b, in regulating the glucose metabolism of non‐small cell lung cancer (NSCLC). In our study, quantitative real‐time polymerase chain reaction (qRT‐PCR) showed that miR‐33b was downregulated in NSCLC tissues and cell lines, which was correlated with increased cell proliferation and colony formation. Overexpression of miR‐33b through miR‐33b mimics transfection suppressed NSCLC proliferation, colony formation, and induced cell‐cycle arrest and apoptosis. Meanwhile, miR‐33b overexpression inhibited glucose metabolism in NSCLC cells. Luciferase reporter assay confirmed that miR‐33b directly binds to the 3′‐untranslated region of lactate dehydrogenase A (LDHA). qRT‐PCR and Western blot analysis showed that miR‐33b downregulated the expression of LDHA. Moreover, introducing LDHA mRNA into cells over‐expressing miR‐33b attenuated the inhibitory effect of miR‐33b on the growth and glucose metabolism in NSCLC cells. Taken together, these results confirm that miR‐33b is an anti‐oncogenic miRNA, which inhibits NSCLC cell growth by targeting LDHA through reprogramming glucose metabolism.

Development of a Novel Six-miRNA-Based Model to Predict Overall Survival Among Colon Adenocarcinoma Patients

“…For example, Feng et al suggested that miR-152 could inhibit cell growth in prostate cancer progression (21). Interestingly, several studies found that miR-33b was a tumor suppressor (22,23). However, miR-33b showed its tumorigenesis and was associated with poor survival in our studies.…”

Non-Coding RNAs in Lung Tumor Initiation and Progression

“…miR-125a and miR-143 have been reported to target the glycolytic enzyme hexokinase 2 (HK2) by downregulation [188]. As for lactate dehydrogenase A, an enzyme in glycolysis responsible for imitation of lactate production, has targets serving as negative regulators include miR-200c [189], miR-33b [190], and miR-449a [191]. Additionally, lncRNA CRYBG3 overexpression has been reported to be associated with LDHA upregulation [192].…”

Effect of gga-miR-155 on cell proliferation, apoptosis and invasion of Marek’s disease virus (MDV) transformed cell line MSB1 by targeting RORA

“…MicroRNAs (miRNAs) are endogenous small noncoding RNA that degrade mRNAs or inhibit translation by binding to their 3′-untranslated regions (3′-UTR), and therefore regulate multiple cellular processes, such as proliferation, cell cycle, apoptosis, migration and metabolism [9][10][11][12][13]. Recent studies have identified several host and viral miRNAs that potentially regulate MDVinduced tumorigenesis [14][15][16][17].…”