MicroRNA‑433 reduces cell proliferation and invasion in non‑small cell lung cancer via directly targeting E2F transcription factor 3

Abstract

MicroRNAs (miRNA/miRs) have been associated with the initiation and progression of non‑small‑cell lung cancer (NSCLC). Hence, a comprehensive understanding of the association between dysregulated miRNAs and NSCLC may contribute to the identification of novel therapeutic methods for patients with NSCLC. MiRNA‑433 (miR‑433) has been reported to be dysregulated in numerous types of human cancers; however, its expression pattern, biological roles and associated mechanisms in NSCLC require further investigation. The present study aimed to detect miR‑433 expression and determine its roles and underlying molecular mechanisms in NSCLC. In the present study, reverse transcription‑quantitative polymerase chain reaction revealed that miR‑433 was significantly downregulated in NSCLC tissues and cell lines. This decreased miR‑433 expression was strongly associated with the tumor node metastasis stage and lymph node metastasis of patients with NSCLC. Cell Counting kit‑8 and cell invasion assays revealed that the resumption of miR‑433 expression decreased the proliferation and invasion of NSCLC cells. Bioinformatics analysis predicted E2F transcription factor 3 (E2F3) as a potential target of miR‑433. Luciferase reporter assay, RT‑qPCR and western blot analysis further demonstrated that E2F3 was a direct target of miR‑433 in NSCLC. E2F3 downregulation induced by small interfering RNA exhibited inhibitory effects similar to those of miR‑433 overexpression in NSCLC cells, and the restored E2F3 expression counteracted the suppressive effects on NSCLC cells induced by miR‑433 overexpression. Therefore, miR‑433 may inhibit the progression of NSCLC, at least in part, by targeting E2F3. The present study indicated that miR‑433 may be investigated as an innovative candidate target for the therapy of patients with this fatal disease.

LncRNA MALAT1 contributes to non-small cell lung cancer progression via modulating miR-200a-3p/programmed death-ligand 1 axis

“…For example, miR-433 inhibits the proliferation and invasion of NSCLC cells by directly targeting E2F3. 10 And miR-182 promotes NSCLC cells by suppressing tumor suppressors FBXW7 and FBXW11. 11 Mounting studies suggest that miR-200a-3p plays a tumor repressive role in multiple tumors, such as liver cancer and esophagus cancer.…”

Genetic Analysis of Human RNA Binding Motif Protein 48 (RBM48) Reveals an Essential Role in U12-Type Intron Splicing

“…For example, mutations in BRCC3, which encodes a cell cycle regulator involved in G2/M phase transition, has been linked to myelodysplastic syndrome (MDS), as well as breast and cervical cancers (Boudreau et al 2007;Huang et al 2015;Zhang, Zhou 2018). Mutations in E2F3 have been associated with retinoblastoma, bladder and lung cancer (Ziebold et al 2001;Wang et al 2017a;Liu et al 2018).…”

<p>Transcription factor E2F1 positively regulates interferon regulatory factor 5 expression in non-small cell lung cancer</p>

“…26 Liu reported that miR-433 inhibit the progression of NSCLC by targeting E2F3. 27 Park indicated that E2F8 is overexpression in LC and is necessary for the growth of LC cells. 28 E2F1 is a transcription factor involved in the regulation of a variety of biological activities, including cell cycle, apoptosis, proliferation, angiogenesis, tumor resistance, infiltration and metastasis.…”