Long non‑coding RNA LINC01748 exerts carcinogenic effects in non‑small cell lung cancer cell lines by regulating the microRNA‑520a‑5p/HMGA1 axis

Abstract

The important functions of long non-coding RNAs in the malignancy of non-small cell lung cancer (NSCLC) has been increasingly highlighted. However, whether LINC01748 functions in a crucial regulatory role still requires further research. The aim of the present study was to investigate the biological roles of LINC01748 in NSCLC. Furthermore, different experiments were utilized to investigate the mechanism of action of LINC01748 in 2 NSCLC cell lines. Reverse transcription-quantitative PCR was used to measure mRNA expression levels. Cell Counting Kit-8 assay, flow cytometry analysis and Transwell and Matrigel assays were also used to analyze, cell viability, apoptosis, and migration and invasion, respectively. A tumor xenograft model was used for in vivo experiments. RNA immunoprecipitation experiments, luciferase reporter assays and rescue experiments were used to investigate the mechanisms involved. Data from The Cancer Genome Atlas dataset and patients recruited into the present study showed that LINC01748 was overexpressed in NSCLC. Patients with high LINC01748 mRNA expression level had shorter overall survival rate compared with that in patients with low LINC01748 mRNA expression level. Then, knockdown of LINC01748 mRNA expression level reduced cell proliferation, migration and invasion, but increased cell apoptosis in vitro . Knockdown of LINC01748 also reduced tumor growth in vivo . Mechanistically, LINC01748 could act as a competing endogenous (ce)RNA to sponge microRNA(miR)-520a-5p, to increase the expression level of the target gene, high mobility group AT-hook 1 (HMGA1) in the NSCLC cell lines. Furthermore, rescue experiments illustrated that the functions exerted by LINC01748 knockdown were negated by miR-520a-5p inhibition or HMGA1 overexpression. In summary, LINC01748 acted as a ceRNA by sponging miR-520a-5p, leading to HMGA1 overexpression, thus increasing the aggressiveness of the NSCLC cells. Accordingly, targeting the LINC01748/miR-520a-5p/HMGA1 pathway may benefit NSCLC therapy.

A Novel Necroptosis-Related lncRNA Signature Predicts the Prognosis of Lung Adenocarcinoma

“…Growing evidence has ascertained that lncRNAs are involved in the progression and metastasis of NSCLC and were associated with the immune pathway ( Pang et al, 2021 ). LINC01748 exerted carcinogenic effects in NSCLC cell lines by regulating the microRNA-520a-5p/HMGA1 axis ( Tan et al, 2022 ). lncRNA-SChLAP1 was verified to induce NSCLC progression and immune evasion by regulating the AUF1/PD-L1 pathway ( Du et al, 2021 ).…”

Non-coding ribonucleic acid-mediated CAMSAP1 upregulation leads to poor prognosis with suppressed immune infiltration in liver hepatocellular carcinoma

“…For example, AC145207.5 (RP11-498C9.15) plays a pivotal role in rheumatoid arthritis by modulating both miRNAs and gene expression ( Dolcino et al, 2019 ). Moreover, LINC01748 regulates the miRNA-520a-5p/HMGA1 axis to exert carcinogenic effects in non-small cell lung cancer ( Tan et al, 2022 ). Collectively, the AC145207.5/LINC01748-miR-101-3p- CAMSAP1 axis has been identified as a potential regulatory pathway in LIHC.…”

High Mobility Group A1 (HMGA1): Structure, Biological Function, and Therapeutic Potential

“…Chemoresistance is a challenging issue in cancer therapy. Numerous studies have shown that HMGA1 can be involved in drug resistance to cisplatin, gefitinib, 5-FU, gemcitabine, and trabectedin in a TGF-β-, pathway-, microRNA-, and lncRNAregulated manner in a variety of tumours, such as NSCLC, gastric cancer, ovarian cancer, glioblastoma, cholangiocarcinoma, colorectal cancer, thyroid cancer, and liposarcoma [65,93,142,[148][149][150][151][152][153]. More importantly, HMGA1 silencing can also reduce self-renewal, dryness and spheroid formation in glioblastoma and colorectal cancer, increasing drug sensitivity [95,142].…”