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miR-7 modulates chemoresistance of small cell lung cancer by repressing MRP1/ABCC1
Huanxin Liu1,2, Xiaoxia Wu2, Jie Huang1
1Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Abstract:
MicroRNAs (miRNAs) represent a class of small non-coding RNAs and have been shown to play important roles in various biological processes including cell growth, differentiation and apoptosis by regulating the target genes. miR-7 has been described not only as a tumour suppressor gene but also as an oncogene in human cancers. The aim of this study was to investigate the functional roles of miR-7 in chemoresistance of SCLC and its underlying mechanism. By using a bioinformatic assay, we found that MRP1/ABCC1 was a potential target gene of miR-7. Expression of miR-7 and MRP1/ABCC1 was examined in 44 SCLC samples by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry methods. Low-level expression of miR-7 was associated significantly with drug responsiveness and overall survival rate of patients with SCLC, but not with gender, age and stage. There was an inverse relationship between miR-7 and MRP1/ABCC1 expression. Downregulation of MRP1/ABCC1 level was revealed after transfection with a miR-7 mimic in H69 AR cells. Transfection of a miR-7 inhibitor into H69 cells restored MRP1/ABCC1 expression. A dual-luciferase reporter assay confirmed that miR-7 targeted predicted sites in the 3'-untranslated region (3'-UTR) of the MRP1/ABCC1 gene. Our data suggested that miR-7 mediated SCLC chemoresistance by repressing MRP1/ABCC1 and may be a prognostic predictor and potential therapeutic target in human SCLC.
Insights
MicroRNA-7 (miR-7) plays a crucial role in small cell lung cancer (SCLC) chemoresistance by targeting the MRP1/ABCC1 gene. Low miR-7 levels correlate with poor drug response and survival in SCLC patients.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs regulating gene expression in biological processes.
- miR-7 exhibits context-dependent roles as a tumor suppressor or oncogene in human cancers.
- Chemoresistance is a major challenge in treating small cell lung cancer (SCLC).
Purpose of the Study:
- To investigate the functional role of miR-7 in SCLC chemoresistance.
- To elucidate the underlying molecular mechanism involving miR-7 and its potential targets.
- To assess miR-7 as a prognostic biomarker and therapeutic target in SCLC.
Main Methods:
- Bioinformatic analysis to identify potential miR-7 targets.
- Quantitative reverse transcription-polymerase chain reaction and immunohistochemistry to analyze miR-7 and MRP1/ABCC1 expression in SCLC samples.
- Cell-based assays (transfection with miR-7 mimic/inhibitor) and dual-luciferase reporter assay to confirm gene targeting.
Main Results:
- MRP1/ABCC1 was identified as a potential target of miR-7.
- Low miR-7 expression was significantly associated with reduced drug responsiveness and overall survival in SCLC patients.
- An inverse relationship between miR-7 and MRP1/ABCC1 expression was observed, with miR-7 repressing MRP1/ABCC1 levels.
Conclusions:
- miR-7 mediates chemoresistance in SCLC by downregulating MRP1/ABCC1 expression.
- miR-7 holds potential as a prognostic predictor for SCLC patients.
- Targeting miR-7 represents a potential therapeutic strategy for overcoming chemoresistance in SCLC.
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