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Published on: March 14, 2019
MIMT1 and LINC01550 are uncharted lncRNAs down-regulated in colorectal cancer
Faramarz Vejdandoust1, Rahmaneh Moosavi2, Nasrin Fattahi Dolatabadi3
1Department of Biology, Azad University, Ashkezar Branch, Yazd, Iran.
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).
Insights
Two long noncoding RNAs (lncRNAs), MIMT1 and LINC01550, were found to be downregulated in colorectal cancer. These lncRNAs may function as tumor suppressors, offering potential new targets for colorectal cancer diagnosis and treatment.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Colorectal cancer (CRC) remains a leading cause of cancer death globally due to incomplete understanding of its molecular basis, hindering early diagnosis and effective treatment.
- While coding transcripts in CRC are extensively studied using high-throughput profiling and datasets like The Cancer Genome Atlas (TCGA), the role of noncoding RNA dysregulation is poorly understood.
- Long noncoding RNAs (lncRNAs) represent a critical, yet under-explored, class of noncoding RNAs with potential implications in cancer development.
Purpose of the Study:
- To identify and evaluate novel long noncoding RNAs (lncRNAs) for their potential role in colorectal cancer (CRC) using a bioinformatics approach.
- To investigate the expression patterns of candidate lncRNAs in CRC tissues compared to adjacent normal tissues.
- To elucidate the potential molecular mechanisms, including competitive endogenous RNA (ceRNA) networks, by which these lncRNAs may regulate CRC.
Main Methods:
- Bioinformatic analysis of The Cancer Genome Atlas (TCGA) RNA-seq data to shortlist potential lncRNAs in colorectal cancer.
- Validation of expression patterns for selected lncRNAs (MIMT1 and LINC01550) using quantitative real-time PCR (qPCR) on in-house clinical samples.
- In silico analysis to predict the formation of competitive endogenous RNA (ceRNA) networks involving LINC01550 and its target genes.
Main Results:
- Bioinformatic analysis identified MER1 Repeat Containing Imprinted Transcript 1 (MIMT1) and Non-Protein Coding RNA 1550 (LINC01550) as potential candidates for further study in colorectal cancer.
- Quantitative real-time PCR (qPCR) confirmed that both MIMT1 and LINC01550 were significantly downregulated in colorectal cancer tumors compared to matched adjacent normal tissues.
- In silico analysis suggested that LINC01550 may participate in a ceRNA network, potentially regulating key colorectal cancer-associated genes such as CELF2, PTBP1, and ELAV1.
Conclusions:
- MIMT1 and LINC01550 are novel long noncoding RNAs (lncRNAs) that exhibit downregulated expression in colorectal cancer.
- These lncRNAs demonstrate potential as tumor suppressor genes in the context of colorectal cancer.
- Further investigation into the roles of MIMT1 and LINC01550 in regulating cancer signaling pathways is warranted for potential diagnostic and therapeutic applications.
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