Identification of lncRNA, miRNA and mRNA expression profiles and ceRNA Networks in small cell lung cancer

BMC Genomics. 2023 Apr 25;24(1):217. doi: 10.1186/s12864-023-09306-4.

Abstract

Background: Small cell lung cancer (SCLC) is a highly lethal malignant tumor. It accounts for approximately 15% of newly diagnosed lung cancers. Long non-coding RNAs (lncRNAs) can regulate gene expression and contribute to tumorigenesis through interactions with microRNAs (miRNAs). However, there are only a few studies reporting the expression profiles of lncRNAs, miRNAs, and mRNAs in SCLC. Also, the role of differentially expressed lncRNAs, miRNAs, and mRNAs in relation to competitive endogenous RNAs (ceRNA) network in SCLC remain unclear.

Results: In the present study, we first performed next generation sequencing (NGS) with six pairs of SCLC tumors and adjacent non-cancerous tissues obtained from SCLC patients. Overall, 29 lncRNAs, 48 miRNAs, and 510 mRNAs were found to be differentially expressed in SCLC samples (|log2[fold change] |> 1; P < 0.05). Bioinformatics analysis was performed to predict and construct a lncRNA-miRNA-mRNA ceRNA network, which included 9 lncRNAs, 11 miRNAs, and 392 mRNAs. Four up-regulated lncRNAs and related mRNAs in the ceRNA regulatory pathways were selected and validated by quantitative PCR. In addition, we examined the role of the most upregulated lncRNA, TCONS_00020615, in SCLC cells. We found that TCONS_00020615 may regulate SCLC tumorigenesis through the TCONS_00020615-hsa-miR-26b-5p-TPD52 pathway.

Conclusions: Our study provided the comprehensive analysis of the expression profiles of lncRNAs, miRNAs, and mRNAs of SCLC tumors and adjacent non-cancerous tissues. We constructed the ceRNA networks which may provide new evidence for the underlying regulatory mechanism of SCLC. We also found that the lncRNA TCONS_00020615 may regulate the carcinogenesis of SCLC.

Keywords: RNA-sequencing (RNA-Seq); Small cell lung cancer (SCLC); TCONS_00020615; ceRNA network; lncRNA; mRNA; miRNA.

MeSH terms

  • Carcinogenesis / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • Lung Neoplasms* / genetics
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neoplasm Proteins / genetics
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Small Cell Lung Carcinoma* / genetics

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger
  • TPD52 protein, human
  • Neoplasm Proteins