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LINC01140 inhibits nonsmall cell lung cancer progression and cisplatin resistance through the miR-4742-5p/TACC1 axis
Yanyun Wang1, Man Li2, Lin Zhang1
1Department of Medical Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Abstract:
Recent studies show that lncRNAs participate in drug resistance and nonsmall cell lung cancer (NSCLC) progression. This study aimed to study the roles and mechanisms of long intergenic nonprotein coding RNA 01140 (LINC01140) in regulating NSCLC progression and drug resistance. Real-time quantitative polymerase chain reaction and western blot analysis were used to detect LINC01140, miR-4742-5p, and transforming acidic coiled-coil 1 (TACC1) expression in NSCLC cells. The interaction between two molecules was examined by luciferase reporter and/or RNA immunoprecipitation assays. Cell invasion, apoptosis, and cisplatin cytotoxicity were assessed by transwell invasion assay, flow cytometry analysis, and CCK-8 assay, respectively. LINC01140 was downregulated and miR-4742-5p was upregulated in NSCLC. LINC01140 inhibited miR-4742-5p expression by competitively binding to miR-4742-5p, while miR-4742-5p targeted TACC1 to inhibit TACC1 expression in NSCLC cells. LINC01140 enrichment repressed the invasive potential and cisplatin resistance and triggered apoptosis, which was reversed by miR-4742-5p overexpression. miR-4742-5p inhibition suppressed cell invasion and cisplatin resistance and accelerated apoptosis in NSCLC cells, while TACC1 silencing abolished these effects. Mechanistically, LINC01140 positively regulated TACC1 expression by sponging miR-4742-5p. In conclusion, LINC01140 inhibited NSCLC progression and cisplatin resistance via functioning as a ceRNA for miR-4742-5p to modulate TACC1.
Insights
Long intergenic nonprotein coding RNA 01140 (LINC01140) suppresses nonsmall cell lung cancer (NSCLC) progression and cisplatin resistance by regulating the miR-4742-5p/TACC1 axis. This finding offers new therapeutic targets for NSCLC treatment.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Long noncoding RNAs (lncRNAs) are implicated in nonsmall cell lung cancer (NSCLC) progression and drug resistance.
- The specific roles of long intergenic nonprotein coding RNA 01140 (LINC01140) in NSCLC remain to be fully elucidated.
Purpose of the Study:
- To investigate the regulatory functions and underlying mechanisms of LINC01140 in NSCLC progression and chemoresistance.
- To explore the interaction between LINC01140, miR-4742-5p, and transforming acidic coiled-coil 1 (TACC1) in NSCLC.
Main Methods:
- Quantitative real-time PCR and western blot assays were employed to measure gene and protein expression.
- Luciferase reporter and RNA immunoprecipitation assays were utilized to confirm molecular interactions.
- Cellular assays including transwell invasion, flow cytometry, and CCK-8 were performed to assess invasion, apoptosis, and drug sensitivity.
Main Results:
- LINC01140 expression was found to be downregulated in NSCLC, while miR-4742-5p was upregulated.
- LINC01140 acts as a competing endogenous RNA (ceRNA) for miR-4742-5p, thereby positively regulating TACC1 expression.
- Overexpression of LINC01140 suppressed NSCLC cell invasion and cisplatin resistance while promoting apoptosis, effects that were reversed by miR-4742-5p.
- Inhibition of miR-4742-5p mimicked the effects of LINC01140, and TACC1 silencing abrogated these changes.
Conclusions:
- LINC01140 plays an inhibitory role in NSCLC progression and cisplatin resistance.
- The LINC01140/miR-4742-5p/TACC1 axis represents a potential therapeutic target for NSCLC treatment.
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