DCLK1, a promising colorectal cancer stem cell marker,regulates tumor progression and invasion through miR-137 and miR-15a dependent manner |
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Authors: | Razi Sepideh Sadeghi Asieh Asadi-Lari Zeynab Tam Kevin J. Kalantari Elham Madjd Zahra |
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Affiliation: | 1.Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran ;2.Department of Pathology, Iran University of Medical Sciences, Tehran, Iran ;3.Department of Biology, University of Toronto, Toronto, Canada ;4.Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada ;5.Department of Molecular Medicine, Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran ; |
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Abstract: | Cancer stem cells (CSCs) are thought to be a major player in tumor initiation, progression, and metastasis. Targeting CSCs for elimination presents a promising therapeutic strategy; however, this approach will require a stronger understanding of CSC biology and identification of CSC-specific markers. The present study was conducted to examine the correlation between DCLK1 and miR-137 and miR-15a levels in colorectal cancer. A total of 222 samples, including 181 colorectal cancer specimens, 24 adenomatosis, and 17 non-adenomatosis colonic polyps, were stained for DCLK1 expression using immunohistochemistry. Also, expression of miR-137 and miR-15a was assessed in colorectal cancer with high and low DCLK1 expression levels. Most colorectal cancer specimens (76%) showed strong expression of DCLK1, whereas only 21% of adenomatous and none of non-adenomatous colonic polyps showed strong DCLK1 expression. A significant difference in DCLK1 expression was found between colorectal cancer, adenomatous, and non-adenomatous colonic polyps (P < 0.001). Higher expression of DCLK1 was more frequently detected in colorectal cases with larger tumor size (P = 0.03), poor differentiation (P = 0.03), and lymph node involvement (P = 0.04). Comparison of miR-137 and miR-15a in colorectal cancer cases revealed a significant inverse correlation with DCLK1 expression (P = 0.03 and P = 0.04, respectively). DCLK1 may act as a candidate marker for colorectal cancer stem cells. The critical role of DCLK1 in colorectal cancer suggests that it may represent an early diagnostic marker and therapeutic target; however, further investigation is warranted. |
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