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DCLK1 通过调节 miR-200c 在结直肠癌肿瘤发生中发挥重要作用。

DCLK1 plays an important role in colorectal cancer tumorgenesis through the regulation of miR-200c.

机构信息

Research center for molecular medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Department of Pathology, Dr. Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Biomed Pharmacother. 2018 Jul;103:301-307. doi: 10.1016/j.biopha.2018.04.042. Epub 2018 Apr 24.

DOI:10.1016/j.biopha.2018.04.042
PMID:29656186
Abstract

Doublecortin-like kinase 1 (DCLK1) is a protein kinase that is known as a specific cancer stem cell (CSC) marker in colorectal cancer (CRC). Deregulation of DCLK1 expression has been reported in various cancers. We measured the protein expression of DCLK1 in 38 CRC and normal colon samples by immunohistochemistry (IHC). HCT-116 and SW-48 cells were transfected with DCLK1 siRNA and analyzed for expression of DCLK1 and miR-200c. The effects of DCLK1 knockdown on cell migration, invasion, sphere-forming, and apoptosis were explored. It was found that DCLK1 protein expression levels were significantly higher in CRC tissue than in normal colon specimens. Silencing of DCLK1 significantly inhibited cell migration, invasion, and sphere-forming potential; it also induced apoptosis as well as increased expression of miR-200c. Furthermore, silencing of miR-200c significantly up-regulated DCLK1 expression. Overall, our data demonstrated that DCLK1 plays an important role in cancer progression and is involved in the regulation of miR-200c expression.

摘要

双皮质激酶 1(DCLK1)是一种蛋白激酶,在结直肠癌(CRC)中被认为是一种特定的癌症干细胞(CSC)标志物。已经有报道称 DCLK1 的表达失调存在于各种癌症中。我们通过免疫组织化学(IHC)方法测量了 38 例 CRC 和正常结肠样本中的 DCLK1 蛋白表达。用 DCLK1 siRNA 转染 HCT-116 和 SW-48 细胞,并分析 DCLK1 和 miR-200c 的表达情况。探讨了 DCLK1 敲低对细胞迁移、侵袭、球体形成和细胞凋亡的影响。结果发现,CRC 组织中 DCLK1 蛋白表达水平明显高于正常结肠标本。沉默 DCLK1 显著抑制细胞迁移、侵袭和球体形成潜能;同时诱导细胞凋亡,并增加 miR-200c 的表达。此外,沉默 miR-200c 可显著上调 DCLK1 的表达。总的来说,我们的数据表明 DCLK1 在癌症进展中发挥重要作用,并参与 miR-200c 表达的调节。

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