Alterations of non-coding RNA expression and mitochondrial biogenesis in colorectal cancer tissue: Possible crosstalk with macrophage polarization

Abstract

Colorectal cancer (CRC) is a common worldwide cancer associated with different genetic changes. The present study aimed to elucidate the possible crosstalk between colorectal cancer-derived non-coding RNAs (ncRNAs), tumor mitochondrial biogenesis, and macrophage polarization in colorectal cancer patients. Fresh tumor tissue samples with adjacent normal tissues were obtained from 62 CRC patients, quantitative real-time PCR (qRT-PCR) was used to detect the tissue expression of long non-coding RNAs (lncRNAs) such as PTENP1, H19, XIST, MALAT1, and HOTAIR as well as microRNA ((miR-133a)), mitochondrial markers as mtDNA copy number and Uncoupling protein 2 (UCP2), macrophage markers (INOS, CD80 and CD163) and other genes as TGFβRII and NRF-2. The expression levels of the 5 studied lncRNAs were upregulated in CRC tissues compared to the adjacent non-cancer tissues. HOTAIR expression was negatively correlated with CD80 (M1-polarization marker) and positively correlated with CD163 (M2-polarization marker) while miR-133a showed opposite association with these macrophage markers. Non-significant increase was observed in the tumor mtDNA copy number which showed a positive correlation with XIST. Moreover, a significant positive correlation was shown between CD163 and UCP2 expressions. Furthermore, TGFβRII expression was directly correlated with some lncRNAs (PTENP1, MALAT1, and HOTAIR) and tumor mtDNA copy number. The study highlighted significant crosstalk between ncRNA (HOTAIR and miR-133a) and M2-polarization. The obtained data suggest the potential roles of HOTAIR, miR-133a, UCP2 and TGFβRII in the development of CRC, suggesting their possible diagnostic and therapeutic potentials in CRC.