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Let‐7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin‐like growth factor 1 receptor
Author(s) -
Samadi Pouria,
Afshar Saeid,
Amini Razieh,
Najafi Rezvan,
Mahdavinezhad Ali,
Sedighi Pashaki Abdolazim,
Gholami Mohammad Hadi,
Saidijam Massoud
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27742
Subject(s) - colorectal cancer , radiosensitivity , cancer research , signal transduction , cancer , microrna , biology , growth factor receptor , radioresistance , cell cycle , radiation therapy , cell growth , growth factor , insulin like growth factor , receptor , cancer cell , medicine , microbiology and biotechnology , gene , genetics
Abnormal expression of various microRNAs (miRNAs), as regulators of biological signaling pathways, has a strong association with cancer resistance to chemotherapy and radiotherapy. The let‐7 family of miRNAs as tumor suppressors have shown to be downregulated in different types of human malignancies including colorectal cancer (CRC). However, the biological function of let‐7 members in the processes of resistance to radiation in CRC has not yet been completely elucidated. Insulin‐like growth factor 1 receptor (IGF‐1R) signaling pathway is amplified in CRC and leads to its progression, development, and also radiation resistance. So, it seems like an attractive target for anticancer therapy. In this study, by using bioinformatics analysis, it has been revealed that IGF‐1R is a direct target of the let‐7e member. Consistent with this, we identified that increased levels of let‐7e in CRC cells reduced IGF‐1R protein level and subsequently its downstream signaling pathways, which resulted in the G1 cell cycle arrest and a significant reduction in the proliferation, survival and also resistance to radiation of CRC cells. Altogether, these results suggested that let‐7e by targeting the IGF‐1R signaling pathway might serve as therapeutics in anticancer therapy.