Dataset Information

Long non-coding RNA LINC01116 is activated by EGR1 and facilitates lung adenocarcinoma oncogenicity via targeting miR-744-5p/CDCA4 axis.

ABSTRACT:

Background

Lung adenocarcinoma (LAD) is one of the most frequently diagnosed pathological categories of human lung cancer. Nevertheless, the link between long non-coding RNA (lncRNA) LINC01116 and LAD remains poorly investigated.

Methods

QRT-PCR and western blot were applied for quantifying the expression of RNAs and proteins. Both functional experiments assays in vitro and xenografts model in vivo were implemented for analyzing LINC01116 function in LAD while molecular relationship among RNAs was investigated via mechanism experiments.

Results

LINC01116 was expressed at an abnormally high level in LAD, which was induced by transcription activator EGR1. LINC01116 depletion restrained proliferation, migration and invasion, yet facilitated apoptosis of LAD cells. MiR-744-5p could bind to LINC01116. MiR-744-5p inhibitor reversed the inhibitory effects of silencing LINC01116 on LAD malignant behaviors. In addition, cell division cycle-associated protein 4 (CDCA4) shared binding sites with miR-744-5p. Silencing LINC01116 elicited decline in CDCA4 mRNA and protein levels. Moreover, CDCA4 up-regulation could counteract the biological effects of LINC01116 knockdown on LAD cells.

Conclusion

Our data revealed that LINC01116 promoted malignant behaviors of LAD cells by targeting miR-744-5p/CDCA4 axis, implying the theoretical potential of LINC01116 as a novel target for LAD treatment.

SUBMITTER: Ren P

PROVIDER: S-EPMC8180037 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Long non‑coding RNAs (lncRNAs) have been implicated in the development and progression of tumors. However, the roles and underlying mechanisms of long intergenic non‑protein coding RNA 1116 (LINC01116), a member of the lncRNA family, in glioma progression are largely unclear. The expression of LINC01116 and microRNA (miR)‑744‑5p in glioma tissues and cells was detected by reverse transcription‑quantitative PCR. The influences of LINC01116 or miR‑744‑5p on cell proliferation and invasion were evaluated by Cell Counting Kit‑8, colony formation and Transwell assays, and western blotting was used to detect the expression of p53 pathway proteins. A dual‑luciferase reporter system was used to locate common binding sites between miR‑744‑5p and LINC01116 or the 3' untranslated region of E3 ubiquitin‑protein ligase Mdm2 (MDM2). RNA immunoprecipitation was used to determine the interactions between RNAs and proteins. Moreover, a xenograft mouse model was constructed to investigate the effects of LINC01116 in vivo, followed by a TdT‑mediated dUTP nick end labeling assay to determine the degree of apoptosis in nude mouse tumors. LINC01116 was found to be highly expressed in glioma tissues, which was associated with a malignant phenotype. LINC01116 promoted the proliferation and invasiveness of glioma cells, and inhibited the p53 pathway by preserving the expression of MDM2 mRNA via miR‑744‑5p sponging. Furthermore, a low degree of miR‑744‑5p expression was observed in glioma tissues, which was negatively associated with the expression of LINC01116. Overexpression of miR‑744‑5p inhibited the proliferation and invasiveness of glioma cells, which was rescued by LINC01116. Finally, LINC01116 knockdown inhibited tumor growth in nude mice. In conclusion, LINC01116 is aberrantly expressed and promotes the progression of glioma by regulating the miR‑744‑5p‑MDM2‑p53 pathway. In future, targeting LINC01116 may therefore be a potential therapeutic approach for patients with glioma.