Integrated whole transcriptome and small RNA analysis revealed multiple regulatory networks in colorectal cancer

Abstract

Colorectal cancer (CRC) remains a global disease burden and a leading cause of cancer related deaths worldwide. The identification of aberrantly expressed messenger RNA (mRNA), long non-coding RNA (lncRNA), and microRNA (miRNA), and the resulting molecular interactions and signaling networks is essential for better understanding of CRC, identification of novel diagnostic biomarkers and potential development of therapeutic interventions. Herein, we performed microRNA (miRNA) sequencing on fifteen CRC and their non-tumor adjacent tissues and whole transcriptome RNA-Seq on six paired samples from the same cohort and identified alterations in miRNA, mRNA, and lncRNA expression. Computational analyses using Ingenuity Pathway Analysis (IPA) identified multiple activated signaling networks in CRC, including ERBB2, RABL6, FOXM1, and NFKB networks, while functional annotation highlighted activation of cell proliferation and migration as the hallmark of CRC. IPA in combination with in silico prediction algorithms and experimentally validated databases gave insight into the complex associations and interactions between downregulated miRNAs and upregulated mRNAs in CRC and vice versa. Additionally, potential interaction between differentially expressed lncRNAs such as H19, SNHG5, and GATA2-AS1 with multiple miRNAs has been revealed. Taken together, our data provides thorough analysis of dysregulated protein-coding and non-coding RNAs in CRC highlighting numerous associations and regulatory networks thus providing better understanding of CRC.

Non‐coding RNAs are correlated to TGF‐β receptor type 2 in patients with colorectal cancer

“…Colorectal cancer is well known to be an etiologically heterogeneous disease, exhibiting expression alterations in multiple molecular pathways contributing to CRC onset and progression. Despite considerable advances with resect to early diagnosis and treatment, CRC screening strategies still remain unsatisfactory 8 . Therefore, it is worth identifying the molecular mechanisms related to CRC pathogenesis.…”

“…[1][2][3][4][5][6][7] Notwithstanding recent improvements in early diagnosis and treatment of CRC, the molecular mechanisms implicating in CRC etiology still remain to be well understood. [8][9][10] Numerous underlying cellular and molecular events are reported to contribute in CRC pathogenesis. [11][12][13] Some reports are focused on the gene expression regulators, in particular, miRNAs and long non-coding RNAs (lncRNAs).…”

“…[11][12][13] Some reports are focused on the gene expression regulators, in particular, miRNAs and long non-coding RNAs (lncRNAs). 8,[14][15][16][17][18][19] Thus, the investigtion of lncRNAs, miRNAs and their target genes enables us to identify molecular events underlying CRC onset and pathogenesis. The transforming growth factor beta (TGF-β) signaling pathway executes key roles in various cellular processes such as proliferation, migration and apoptosis through transmembrane-related type I and type II serine/threonine kinase receptors.…”

“…Colorectal cancer (CRC) is the commonest tumor worldwide that accounts for the high mortality and morbidity rate 1–7 . Notwithstanding recent improvements in early diagnosis and treatment of CRC, the molecular mechanisms implicating in CRC etiology still remain to be well understood 8–10 . Numerous underlying cellular and molecular events are reported to contribute in CRC pathogenesis 11–13 .…”

“…Numerous underlying cellular and molecular events are reported to contribute in CRC pathogenesis 11–13 . Some reports are focused on the gene expression regulators, in particular, miRNAs and long non‐coding RNAs (lncRNAs) 8,14–19 . Thus, the investigtion of lncRNAs, miRNAs and their target genes enables us to identify molecular events underlying CRC onset and pathogenesis.…”