Haolei Tan1,2,3, Gangcai Zhu4, Li She1,2, Ming Wei1,2, Yunyun Wang1,2, Leiming Pi1,2, Changhan Chen1,2, Diekuo Zhang1,2, Pingqing Tan3, Jie Chen3, Donghai Huang1,2, Yongquan Tian1,2, Yong Liu1,2, Xin Zhang1,2. 1. Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University87 Xiangya Road, Changsha 410008, Hunan, People's Republic of China. 2. Otolaryngology Major Disease Research Key Laboratory of Hunan Province87 Xiangya Road, Changsha 410008, Hunan, People's Republic of China. 3. Department of Head and Neck Surgery, Hunan Cancer Hospital, The Affiliated Tumor Hospital of Xiangya Medical School, Central South University283 Tongzipo Road, Changsha 410013, Hunan, People's Republic of China. 4. Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University139 Renmin Road, Changsha 410011, Hunan, People's Republic of China.
Abstract
PURPOSE: MicroRNAs function through regulating specific target mRNA expression and then participate in the development and progression of diverse human cancers. MiR-98 shows aberrant expression and dysfunction in tumors. However, its clinical significance and exact role in squamous cell carcinoma of the head and neck (SCCHN) remain elusive. METHODS: MiR-98 expression was examined by qRT-PCR and correlated with clinicopathological variables and prognosis in SCCHN patients. Effects of miR-98 on epithelial-mesenchymal transition (EMT) and the malignant phenotypes of SCCHN were studied. Finally, the role of target gene metadherin (MTDH) in miR-98 mediated effects were assayed. RESULTS: Our results demonstrated that miR-98, as an endogenous inhibitor of MTDH via directly binding to its 3'-untranslated region (UTR) region, decreased significantly in SCCHN tissues. Decreased miR-98 expression was negatively correlated with T classification, clinical stage, lymph node metastasis and a shorter survival status in SCCHN patients. Loss-of-function and gain-of-function analyses confirmed that miR-98 inhibited cell proliferation, migration and invasion of SCCHN cells in vitro. Moreover, miR-98 repression led to increased MTDH expression and induced EMT alteration. Importantly, ectopic expression of MTDH partially reversed the effects caused by miR-98 overexpression. CONCLUSIONS: Our study identifies that miR-98 serves as a suppressor in SCCHN progression via targeting oncogene MTDH.
PURPOSE: MicroRNAs function through regulating specific target mRNA expression and then participate in the development and progression of diverse humancancers. MiR-98 shows aberrant expression and dysfunction in tumors. However, its clinical significance and exact role in squamous cell carcinoma of the head and neck (SCCHN) remain elusive. METHODS:MiR-98 expression was examined by qRT-PCR and correlated with clinicopathological variables and prognosis in SCCHN patients. Effects of miR-98 on epithelial-mesenchymal transition (EMT) and the malignant phenotypes of SCCHN were studied. Finally, the role of target gene metadherin (MTDH) in miR-98 mediated effects were assayed. RESULTS: Our results demonstrated that miR-98, as an endogenous inhibitor of MTDH via directly binding to its 3'-untranslated region (UTR) region, decreased significantly in SCCHN tissues. Decreased miR-98 expression was negatively correlated with T classification, clinical stage, lymph node metastasis and a shorter survival status in SCCHN patients. Loss-of-function and gain-of-function analyses confirmed that miR-98 inhibited cell proliferation, migration and invasion of SCCHN cells in vitro. Moreover, miR-98 repression led to increased MTDH expression and induced EMT alteration. Importantly, ectopic expression of MTDH partially reversed the effects caused by miR-98 overexpression. CONCLUSIONS: Our study identifies that miR-98 serves as a suppressor in SCCHN progression via targeting oncogene MTDH.
Entities:
Keywords:
MTDH; MicroRNA-98; Squamous cell carcinoma of the head and neck; metastasis; prognosis