Journal
GENOMICS
Volume 113, Issue 3, Pages 1114-1126Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygeno.2020.12.045
Keywords
Small cell lung cancer (SCLC); Methylation modifications; Epigenetic signature; Chemotherapy insensitivity; lncRNA-miRNA-mRNA network
Funding
- National Natural Science Foundation of China [81802255]
- Young Talents in Shanghai [2019QNBJ]
- 'Dream Tutor' Outstanding Young Talents Program [fkyq1901]
- Clinical Research Project of Shanghai Pulmonary Hospital [fk18005]
- Key Discipline in 2019 (oncology)
- Project of Shanghai Municipal Science and Technology Commission (Project of Municipal Science and Technology Commission)
- Scientific research project of Shanghai Pulmonary Hospital [fkcx1903]
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This study utilized high-throughput sequencing technologies to investigate SCLC patients and validated the predictive effects of differentially methylated genes in SCLC cell lines. Differential methylation patterns were identified between chemo-sensitive and chemo-insensitive groups, suggesting potential for predicting chemotherapy response in SCLC.
In the study, Methylated DNA immunoprecipitation sequencing, RNA sequencing, and whole-exome sequencing were employed to clinical small cell lung cancer (SCLC) patients. Then, we verified the therapeutic predictive effects of differentially methylated genes (DMGs) in 62 SCLC cell lines. Of 4552 DMGs between chemo-sensitive and chemo-insensitive group, coding genes constituted the largest percentage (85.08%), followed by lncRNAs (10.52%) and miRNAs (3.56%). Both two groups demonstrated two methylation peaks near transcription start site and transcription end site. Two lncRNA-miRNA-mRNA networks suggested the extensive genome connection between chemotherapy efficacy-related non-coding RNAs (ncRNAs) and mRNAs. Combing miRNAs and lncRNAs could effectively predict chemotherapy response in SCLC. In addition, we also verified the predictive values of mutated genes in SCLC cell lines. This study was the first to evaluate multiple drugs efficacy-related ncRNAs and mRNAs which were modified by methylation in SCLC. DMGs identified in our research might serve as promising therapeutic targets to reverse drugs-insensitivity by complex lncRNA-miRNA-mRNA mechanisms in SCLC.
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