DCLK1 Inhibition Sensitizes Colorectal Cancer Cells to Radiation Treatment.

Autor:	Mohammadi C; Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran., Mahdavinezhad A; Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran., Saidijam M; Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran., Bahreini F; Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran., Sedighi Pashaki A; Mahdieh Radiotherapy and Brachytherapy Charitable Center, Hamadan, Iran., Gholami MH; Mahdieh Radiotherapy and Brachytherapy Charitable Center, Hamadan, Iran., Najafi R; Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Jazyk:	angličtina
Zdroj:	International journal of molecular and cellular medicine [Int J Mol Cell Med] 2021 Winter; Vol. 10 (1), pp. 23-33. Date of Electronic Publication: 2021 May 22.
DOI:	10.22088/IJMCM.BUMS.10.1.23
Abstrakt:	Colorectal cancer (CRC) is one of the most prevalent diagnosed cancers and a common cause of cancer-related mortality. Despite effective clinical responses, a large proportion of patients undergo resistance to radiation therapy. Therefore, the identification of efficient targeted therapy strategies would be beneficial to overcome cancer radioresistance. Doublecortin-like kinase 1 (DCLK1) is an intestinal and pancreatic stem cell marker that showed overexpression in a variety of cancers. The transfection of DCLK1 siRNA to ‎normal HCT-116 cells was performed, and then cells were irradiated with X-rays. The effects of DCLK1 inhibition on cell survival, apoptosis, cell cycle, DNA damage response (ATM and γH2AX proteins), epithelial-mesenchymal transition (EMT) related genes (vimentin, N-cadherin, and E-cadherin), cancer stem cells markers ( CD44 , CD133 , ALDH1 , and BMI1 ), and β-catenin signaling pathway (β-catenin) were evaluated. DCLK1 siRNA downregulated DCLK1 expression in HCT-116 cells at both mRNA and protein levels (P < 0.01). Colony formation assay showed a significantly reduced cell survival in the DCLK1 siRNA transfected group in comparison with the control group following exposure to 4 and 6 Gy doses of irradiation (P <0.01). Moreover, the expression of cancer stem cells markers (P <0.01), EMT related genes (P <0.01), and DNA repair proteins including pATM (P <0.01) and γH2AX (P <0.001) were significantly decreased in the transfected cells in comparison with the nontransfected group after radiation. Finally, the cell apoptosis rate (P <0.01) and the number of cells in the G0/G1 phase in the silencing DCLK1 group was increased (P <0.01). These findings suggest that DCLK1 can be considered a promising therapeutic target for the treatment of radioresistant human CRC. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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