DCLK1, a promising colorectal cancer stem cell marker, regulates tumor progression and invasion through miR-137 and miR-15a dependent manner

被引:16
|
作者
Razi, Sepideh [1 ]
Sadeghi, Asieh [2 ]
Asadi-Lari, Zeynab [3 ]
Tam, Kevin J. [4 ]
Kalantari, Elham [1 ]
Madjd, Zahra [1 ,2 ,5 ]
机构
[1] Iran Univ Med Sci, Oncopathol Res Ctr, Tehran, Iran
[2] Iran Univ Med Sci, Dept Pathol, Tehran, Iran
[3] Univ Toronto, Dept Biol, Toronto, ON, Canada
[4] Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC, Canada
[5] Iran Univ Med Sci, Dept Mol Med Adv Technol Med, Tehran, Iran
关键词
Colorectal cancer; Cancer stem cells; DCLK1; MiR-137; miR-15a; EXPRESSION; MICRORNAS; PROLIFERATION; DOUBLECORTIN; INHIBITION; ARREST; GROWTH; CD44;
D O I
10.1007/s10238-020-00665-w
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 andP = 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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页码:139 / 147
页数:9
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