Transcriptome Sequencing reveals the expressed profiles of mRNA and ncRNAs and regulate network via ceRNA mediated molecular mechanism of lung adenocarcinoma bone metastasis in Xuanwei

Transl Cancer Res. 2021 Jan;10(1):73-87. doi: 10.21037/tcr-20-2376.

Abstract

Background: The most ordinary subtype of lung cancer is lung adenocarcinoma (LuAC), which is characterized by strong metastatic ability. And LuAC rates in Xuanwei leads to the poor prognosis and high death rate. In this study, we systematically explored the molecular mechanism of LuAC bone metastasis in Xuanwei by transcriptome sequencing.

Methods: RNA Sequencing was conducted to explore the noncoding RNAs (ncRNAs) expression profiles in primary LuAC and LuAC bone metastasis. We identified differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), lncRNAs (DElncRNAs) and circRNAs (DEcircRNAs). Bioinformatics analyses the possible relationships and functions of the LuAC bone metastasis-related competing endogenous RNA (ceRNA). And qRT-PCR was performed to evaluate the expression of these differently expressed genes in serum.

Results: A total of 2,141 DEmRNAs, 43 DEmiRNAs, 136 DElncRNAs and 706 DEcircRNAs were identified in the Xuanwei patients with primary LuAC vs. LuAC bone metastasis, respectively. The circRNA/miRNA/mRNA and lncRNA/miRNA/mRNA networks of LuAC in Xuanwei with bone metastasis were built, and the gene expression mechanisms regulated by ncRNAs were unveiled via the ceRNA regulatory networks. We observe that lncRNA (ADAMTS9-AS2, TEX41, DLEU2, LINC00152)-miR-223-3p-SCARB1 and hsa_circ_0000053-miR-196a-5p/miR-196b-5p-HOXA5 ceRNA networks might play an important role in bone metastasis of Xuanwei LuAC.

Conclusions: We comprehensively identified ceRNA regulatory networks of LuAC in Xuanwei with bone metastasis as well as revealed the contribution of different ncRNAs expression profiles. Our data demonstrate the association between mRNAs and ncRNAs in the metastasis mechanism of LuAC in Xuanwei with bone metastasis.

Keywords: RNA sequencing; Xuanwei lung adenocarcinoma (Xuanwei LuAC); bone metastasis; ceRNA; mRNA; ncRNAs.