miR-496, miR-1185, miR-654, miR-3183 and miR-495 are downregulated in colorectal cancer cells and have putative roles in the mTOR pathway

Naif Alqurashi; Saeed M Hashimi; Faisal Alowaidi; Saso Ivanovski; Amro Farag; Ming Q Wei

doi:10.3892/ol.2019.10508

miR-496, miR-1185, miR-654, miR-3183 and miR-495 are downregulated in colorectal cancer cells and have putative roles in the mTOR pathway

Oncol Lett. 2019 Aug;18(2):1657-1668. doi: 10.3892/ol.2019.10508. Epub 2019 Jun 21.

Authors

Naif Alqurashi¹, Saeed M Hashimi¹, Faisal Alowaidi², Saso Ivanovski³, Amro Farag³, Ming Q Wei⁴

Affiliations

¹ Department of Basic Science, Deanship of Preparatory Year and Supporting Studies, and Department of Stem Cells, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia.
² Department of Pathology and Laboratory Medicine, College of Medicine and University Hospitals, King Saud University, Riyadh 11451, Saudi Arabia.
³ School of Dentistry, The University of Queensland, Brisbane, QLD 4006, Australia.
⁴ Division of Molecular and Gene Therapies, School of Medical Science, Griffith University, Gold Coast, QLD 4222, Australia.

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by suppressing the target mRNA and inhibiting translation in order to regulate multiple biological processes. miRNAs play important roles as oncogenes or tumor suppressors in the development of various types of human cancer. The regulation of mammalian target of rapamycin (mTOR) by miRNAs has been studied in several types of cancer, including colorectal cancer (CRC). However, to the best of our knowledge, only limited information regarding the function of miRNAs in human CRC is available. In the present study, the expression of 22 miRNAs in CRC cell lines were investigated in regard to key genes in the mTOR pathway. Initially, it was revealed that mTOR, regulatory-associated protein of mTOR complex I and rapamycin-intensive companion of mTOR were overexpressed in CRC cell lines when compared with a normal colorectal cell line. Subsequently, putative miRNA-mRNA associations were identified via multiple miRNA target prediction programs. The expression levels for the candidate miRNAs were validated using quantitative real-time polymerase chain reaction. Expression analysis revealed that, among 20 miRNAs, five miRNAs (miR-496, miR-1185, miR-654, miR-3183 and miR-495) exhibited significant downregulation in association with the mTOR signaling pathway. Taken together, the results from the present study suggest that several miRNAs that are associated with CRC, with possible roles in mTOR signaling, may have potential therapeutic or diagnostic benefits in CRC treatment.

Keywords: colorectal cancer; mammalian target of rapamycin; microRNA; rapamycin-insensitive companion of mammalian target of rapamycin; regulatory-associated protein of mammalian target of rapamycin complex 1.