LncRNA MEG3 inhibits non‑small cell lung cancer via interaction with DKC1 protein

Abstract

Long non-coding RNA (lncRNA) MEG3 is a key biomarker and therapeutic target in lung cancer; however, its underlying molecular mechanism in lung cancer progression remains unclear. The present study demonstrated a novel regulatory axis in lung cancer, lncRNA MEG3/dyskeratosis congenita 1 (DKC1), and further investigated the effects and molecular mechanism of lncRNA MEG3/DKC1 in lung cancer. RT-qPCR and western blot analysis were performed to determine gene and protein expression levels. The RNA immunoprecipitation assay was performed to verify binding between lncRNA MEG3 and DKC1. Flow cytometry analysis was performed to assess cell apoptosis, while the Cell Counting Kit-8 assay was performed to determine cell viability. Transwell and wound healing assays were performed to assess cell invasion and migration, respectively. Telomerase activity was measured using the quantitative TeloTAGGG Telomerase PCR-ELISA kit. The results demonstrated that lncRNA MEG3 was downregulated, while its binding protein, DKC1, was upregulated in lung cancer cells. Furthermore, lncRNA MEG3 inhibited cell proliferation, migration, invasion and telomerase activity in A549 cells by downregulating DKC1. lncRNA MEG3 inhibited non-small cell lung cancer progression by inhibiting telomere function, cell proliferation, telomerase activity, cell migration and invasion via regulation of the DKC1 protein expression. LncRNA MEG3/DKC1 was identified as a novel dual-directional regulatory axis in the present study, acting as a promising target for the treatment of lung cancer.

Research progress regarding long-chain non-coding RNA in lung cancer: a narrative review

“…LncRNA MEG3 can regulate the expression of BRCA1 through competitively binding to microRNA-7-5p ( 66 ). LncRNA MEG3 inhibited cell proliferation, migration, invasion and telomerase activity by downregulating DKC1 ( 67 ). In addition, lncRNA-MEG3 is lowly expressed in NSCLC and affects the immunity and autophagy of NSCLC cells by regulating the miR-543/IDO signaling pathway ( 68 ).…”

Regulation of Long Non-Coding RNAs by Plant Secondary Metabolites: A Novel Anticancer Therapeutic Approach

“…lncRNA MEG3 has been downregulated in non-small cell lung cancer and has a close relation with poor prognosis in patients. Its overexpression in A549 cells could inhibit invasion, migration, proliferation, and telomerase activity by downregulating Dyskeratosis congenita 1 (DKC1) [ 89 ]. DKC1 is an essential subunit of ribonucleoprotein telomerase which plays an important role in the stabilization and activity of telomerase [ 90 ].…”

Upregulated expression of long non-coding RNA MEG3 serves as a prognostic biomarker in severe pneumonia children and its regulatory mechanism

“…Aberrant expression of MEG3 modulates the amount of Th17 and influences Treg/Th17 balance in asthma by combining miRNA-17 [ 11 ]. Besides, MEG3 alters the proliferation and invasion of lung cancer cells and plays as a promising target in lung cancer [ 12 ]. In a previous publication, MEG3 is also expressed at higher levels in epithelial cells separated from patients with idiopathic pulmonary fibrosis [ 13 ].…”