MIMT1 and LINC01550 are uncharted lncRNAs down-regulated in colorectal cancer

Abstract

Incomplete knowledge of the molecular basis of colorectal cancer, with subsequent limitations in early diagnosis and effective treatment, has contributed to this form of malignancy becoming the second most common cause of cancer-related death worldwide. With the advances in high-throughput profiling techniques and the availability of public data sets such as The Cancer Genome Atlas Program (TCGA), a broad range of coding transcripts have been profiled and their underlying modes of action have been mapped. However, there is still a huge gap in our understanding of noncoding RNA dysregulation. To this end, we used a bioinformatics approach to shortlist and evaluate yet-to be-profiled long noncoding RNAs (lncRNAs) in colorectal cancer. We analysed the TCGA RNA-seq data and followed this by validating the expression patterns using a qPCR technique. Analysing in-house clinical samples, the real-time PCR method revealed that the shortlisted lncRNAs, that is MER1 Repeat Containing Imprinted Transcript 1 (MIMT1) and Non-Protein Coding RNA 1550 (LINC01550), were down-regulated in colorectal cancer tumours compared with the paired adjacent normal tissues. Mechanistically, the in silico results suggest that LINC01550 could form a complex competitive endogenous RNA (ceRNA) network leading to the subsequent regulation of colorectal cancer-related genes, such as CUGBP Elav-Like Family Member (CELF2), Polypyrimidine Tract Binding Protein 1 (PTBP1) and ELAV Like RNA Binding Protein 1 (ELAV1). The findings of this work indicate that MIMT1 and LINC01550 could be novel tumour suppressor genes that can be studied further to assess their roles in regulating the cancer signalling pathway(s).

Keywords: LINC01550; MIMT1; ceRNA; colorectal cancer; long noncoding RNA.

FIGURE 1

Schematic flow diagram of the study.

FIGURE 2

Analysis of (A) MIMT1 and (B) LINC01550 expression in the paired in‐house colorectal cancer samples, (n = 25), ** represents p‐values <.01, *** represents p‐values <.0001, Mann–Whitney test. The association analysis between the patients' sex status and expression level of (C) MIMT1 (p‐value = .569) and (D) LINC01550 (p‐value = .180), (n = 25), Mann–Whitney test.

FIGURE 3

Association analysis between the patients' tumour size and expression level of (A) MIMT1, (p‐value = .328) and (B) LINC01550 (p‐value = .294), (n = 25), Kruskal–Wallis test. The association analysis between the patients' lymph node metastasis status and expression level of (C) MIMT1 (p‐value = .631) and (D) LINC01550 (p‐value = .711), (n = 25), Mann–Whitney test.

FIGURE 4

Association analysis between the patients' tumour grade and expression level of (A) MIMT1, (p‐value = .184) and (B) LINC01550 (p‐value = .589), (n = 25), Mann–Whitney test. The association analysis between the patients' tumour stage and expression level of (C) MIMT1, (p‐value = .749) and (D) LINC01550 (p‐value = .254), (n = 25), Mann–Whitney test.