Abstract
Colorectal cancer (CRC) is one of the leading cancer-related causes of death in the world. Recently, downregulation of microRNA-497 (miR-497) has been observed in CRC tissues. In this study, we found that miR-497 expression levels were downregulated in human CRC specimens compared to the adjacent normal tissues. MiR-497 expression levels were strongly correlated with clinical stages and lymph node metastases. Furthermore, kinase suppressor of ras 1 (KSR1), a known oncogene, was a direct target of miR-497, and KSR1 expression levels were inversely correlated with miR-497 expression levels in human CRC specimens. Overexpression of miR-497 inhibited cell proliferation, migration, invasion and increased chemosensitivity to 5-fluorouracil treatment, whereas forced expression of KSR1 had the opposite effect. Taken together, these results revealed that lower miR-497 levels in human CRC tissues induce KSR1 expression which is associated with CRC cancer occurrence, advanced stages, metastasis and chemoresistance. Lower miR-497 levels may be a potential biomarker for CRC advanced stages and treatment response.
Highlights
Colorectal cancer (CRC) is one of the most prevalent carcinomas throughout the world, with an estimated one million new cases and half million mortalities each year [1, 2]
To compare miR-497 expression levels among different clinical stages, we found that its expression levels in tumor tissues were correlated with the clinical stages of CRC patients
Cell growth rate in the presence of 5-fluorouracil was assayed using CCK-8 proliferation assay at different time points, we found that forced expression of kinase suppressor of ras 1 (KSR1) resulted in more resistance to 5-fluorouracil treatment in miR-497-overexpressing CRC cells (Figure 5B)
Summary
Colorectal cancer (CRC) is one of the most prevalent carcinomas throughout the world, with an estimated one million new cases and half million mortalities each year [1, 2]. The advances of diagnostic and therapeutic approaches have greatly improved long-term survival of CRC, but a significant proportion of patients still develop into drug resistance, relapse and poor outcomes [5,6,7]. Colorectal cancer arises from a series of genetic and epigenetic alterations that may inactivate tumor suppressor genes or/and activate oncogenes [8]. The basic mechanisms underlying CRC initiation and progression remain largely unknown. Better understanding of the molecular mechanisms underlying carcinogenesis, progression and drug resistance in CRC would be helpful in improving diagnosis, therapy and prevention
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
