Long Non-coding RNA LINC00628 Interacts Epigenetically with the LAMA3 Promoter and Contributes to Lung Adenocarcinoma

Abstract

Long non-coding RNAs (lncRNAs) have emerged as key regulators of cellular progress in lung adenocarcinoma. In this study, to identify cancer-related lncRNAs and genes, we screened for those lncRNAs that were differentially expressed in lung adenocarcinoma, which revealed LINC00628 overexpression and low expression of laminin subunit alpha 3 (LAMA3). This was further validated in the cancerous tissues from patients diagnosed with lung adenocarcinoma. Thereafter, we explored the functional relevance of LINC00628 and LAMA3 in lung adenocarcinoma by analyzing the recruitment of DNA methyltransferase (DNMT) and the cellular processes of lung adenocarcinoma cells following treatments that induced LINC00628 overexpression or LINC00628 silencing or with 5-azacytidine (5-Aza, a DNMT inhibitor). The results showed that LINC00628 silencing decreased cell proliferation, migration, and invasion as well as the drug resistance of lung adenocarcinoma cells to vincristine (VCR). The results were opposite in the cells with LAMA3 demethylation induced by 5-Aza treatment. Further research indicated that LINC00628 recruited DNMT1, DNMT3A, and DNMT3B to promote the methylation of LAMA3 promoter, thereby decreasing its expression. Moreover, an in vivo experiment was performed in nude mice to assess the tumor growth ability and drug resistance of human lung adenocarcinoma cells. It was observed that LINC00628 silencing or 5-Aza treatment inhibited the in vivo tumor growth ability of the human lung adenocarcinoma cells and reduced their resistance to VCR. Altogether, our results provide evidence of a mechanism by which LINC00628 silencing exerts an inhibitory role in lung adenocarcinoma by modulating the DNA methylation of LAMA3, indicative of a novel molecular target for treatment of lung adenocarcinoma patients showing resistance to VCR.

Identification of a Ferroptosis-Related LncRNA Signature as a Novel Prognosis Model for Lung Adenocarcinoma

“…LINC00968 is under expressed in LUAD and inhibits tumor cell growth through the linc00968/miR-9-5p/CPEB3 ( 56 ) and miR-21-5p/SMAD7 ( 57 ) axes.LINC00628 is a tumor suppressor gene in multiple tumors, including gastric cancer ( 58 ), breast cancer ( 59 ), osteosarcoma ( 60 ) and hepatocellular carcinoma(HCC) ( 61 ). However, it was found that LINC00628 silencing inhibited proliferation, migration, and invasion of LUAD cells ( 62 ),which is consistent with our findings that LINC00628 acts as a risk factor for LUAD. Yonathan Brhane et al.…”

Identification of Expression Patterns and Potential Prognostic Significance of m5C-Related Regulators in Head and Neck Squamous Cell Carcinoma

“…Another study demonstrated that NSUN5 epigenetic inactivation is a hallmark of long-term survival for patients with glioma (50). Additionally, emerging research has indicated that DNMT1 and DNMT3A share oncogene affections (58,59). These results agree well with the constructed risk model using the three risk genes.…”

N-Glycoproteomics Study of Putative N-Glycoprotein Biomarkers of Drug Resistance in MCF-7/ADR Cells

“…LAMA3 was down-regulated in lung adenocarcinoma with over expression of long non-coding RNA LINC00628. Xu et al (2019) illustrated the mechanism that highly expressed LINC00628 bound to promoter region of LAMA3 gene, resulting in the increase of methylase. With the promotion of LAMA3 promoter methylation, LAMA3 expression was inhibited, then tumor invasion, migration and drug resistance might occur (Xu et al 2019).…”