MiR‐34b‐3p represses cell proliferation, cell cycle progression and cell apoptosis in non‐small‐cell lung cancer (NSCLC) by targeting CDK4

Abstract

Lung cancer is the most common incident cancer, with a high mortality worldwide, and non‐small‐cell lung cancer (NSCLC) accounts for approximately 85% of cases. Numerous studies have shown that the aberrant expression of microRNAs (miRNAs) is associated with the development and progression of cancers. However, the clinical significance and biological roles of most miRNAs in NSCLC remain elusive. In this study, we identified a novel miRNA, miR‐34b‐3p, that suppressed NSCLC cell growth and investigated the underlying mechanism. miR‐34b‐3p was down‐regulated in both NSCLC tumour tissues and lung cancer cell lines (H1299 and A549). The overexpression of miR‐34b‐3p suppressed lung cancer cell (H1299 and A549) growth, including proliferation inhibition, cell cycle arrest and increased apoptosis. Furthermore, luciferase reporter assays confirmed that miR‐34b‐3p could bind to the cyclin‐dependent kinase 4 (CDK4) mRNA 3′‐untranslated region (3′‐UTR) to suppress the expression of CDK4 in NSCLC cells. H1299 and A549 cell proliferation inhibition is mediated by cell cycle arrest and apoptosis with CDK4 interference. Moreover, CDK4 overexpression effectively reversed miR‐34‐3p‐repressed NSCLC cell growth. In conclusion, our findings reveal that miR‐34b‐3p might function as a tumour suppressor in NSCLC by targeting CDK4 and that miR‐34b‐3p may, therefore, serve as a biomarker for the diagnosis and treatment of NSCLC.

PD-1 inhibitor inducing exosomal miR-34a-5p expression mediates the cross talk between cardiomyocyte and macrophage in immune checkpoint inhibitor–related cardiac dysfunction

“…44 This study found that ICIs induced the accumulation of miR-34a-5p in the exosomes and its transfer to cardiomyocytes, thus leading to cardiac senescence. miR-34 has been reported to promote cell cycle arrest, 45 coincident with the finding of the present study that exosomal-delivered miR-34a-5p inhibited cell cycle in the G0/G1 phase. miR-34a triggers senescence partly through the genetic inhibition of PNUTS in cardiomyocytes.…”

Non-Coding RNAs in Lung Tumor Initiation and Progression

“…For example, downregulated miR-545 expression in NSCLC enhances expressions of CDK4 leading to enhanced cell proliferation [146]. Similarly, other tumor suppressive miRNAs including miR-486-5p [147], miR-613 [148], miR-340 [149], and miR-34b-3p [150] upregulate expression of CDK4 in NSCLC. Although few studies of non-coding RNAs involved in the immortalization process have been demonstrated in lung cancer, the aforementioned data suggests that these links could provide valuable therapeutic targets.…”

MiR‐148b suppressed non‐small cell lung cancer progression via inhibiting ALCAM through the NF‐κB signaling pathway

“…Feng and colleagues reported that miR‐34b exhibited a repressive effect on NSCLC cell proliferation and promotion effect on cell apoptosis . MiRNAs have drawn great attention to the diagnosis, prognosis and metastasis of tumors. Here, in our study, miR‐148b expression was found to be downregulated in NSCLC and was closely associated with clinical significance.…”

“…For instance, upregulation of miR‐221, −21, −421 were found in NSCLC and participated in the proliferation, metastasis and apoptosis as oncogenes. Moreover, downregulation of miR‐612, −621, −34b have been proven to be associated with the development of NSCLC . Wang et al .…”