Loss of miR-125b-1 contributes to head and neck cancer development by dysregulating TACSTD2 and MAPK pathway.
Loss of miR-125b-1 contributes to head and neck cancer development by dysregulating TACSTD2 and MAPK pathway.
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MicroRNAs (miRNAs) have important roles in the initiation and progression of human cancer, but their role in head and neck cancer development and progression is not well defined. We aimed to determine whether specific miRNAs and their target mRNAs contribute to head and neck cancer pathogenesis and progression. To identify miRNAs associated with head and neck squamous cell carcinomas (HNSCCs), we analyzed HNSCC cell lines, normal head and neck tissues and normal keratinocytes by miRNA profiling; a group of differentially expressed miRNAs was identified, which includes miR-125b. Decreased expression of miR-125b is known to occur in epithelial cancers and many target mRNAs for this miR have been reported. We found decreased expression of miR-125b-1 and hypermethylation of its promoter in HNSCC compared with its non-malignant counterpart. The TACSTD2 (also known as TROP2) gene was identified and validated as a direct target of miR-125b-1. Abnormal expression of TACSTD2 cell-surface glycoprotein has been reported in most epithelial tumors, and the overexpressions of this mRNA and protein product has been considered a useful tumor marker. We report that miR-125b-1 causes mitogen-activated protein kinase pathway dysfunction through regulation of TACSTD2 expression. Thus, loss of miR-125b-1 may have a key role in the pathogenesis and progression of squamous cell carcinomas of head and neck and possibly of other tumors.
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高迁移率A2是头颈鳞状细胞癌中miRNA-98的靶标。
影响因子：
37.3
作者：
Hebert, Carla;Norris, Kathleen;Scheper, Mark A;Nikitakis, Nikolaos;Sauk, John J
通讯作者：
Sauk, John J
DOI：
10.1158/1078-0432.ccr-08-3131
发表时间：
2009-04-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Avissar M;Christensen BC;Kelsey KT;Marsit CJ
通讯作者：
Marsit CJ
影响因子：
4.2
作者：
Kimura, Sotai;Naganuma, Seiji;Itoh, Hiroshi
通讯作者：
Itoh, Hiroshi
影响因子：
13.5
作者：
Liang, Linhui;Wong, Chun-Ming;He, Xianghuo
通讯作者：
He, Xianghuo
影响因子：
11.2
作者：
Kozaki, Ken-ichi;Imoto, Issei;Inazawa, Johji
通讯作者：
Inazawa, Johji