Study on the Interplay Between Twist1 and Other EMT Regulators Through microRNA-29 Family.

Study Overview
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Brief Summary
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Investigation of the molecular mechanism and clinical significance of the interplay between Twist1 and other EMT regulators through microRNA-29 family.

Detailed Description
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Head and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer deaths worldwide, and it ranks the fourth male cancer-related death in Taiwan. In HNSCC, invasiveness and metastasis of cancer cells contribute to the major cause of mortality; therefore, elucidation of the mechanism and development of new strategies against metastasis is the utmost importance in treating advanced HNSCC. Epithelial-mesenchymal transition (EMT) is a process by which epithelial cells lose their polarity and are converted to a mesenchymal phenotype, and recently is considered as the major mechanism for cancer metastasis. The initiation of EMT is hallmarked by suppression of the intercellular junctional protein E-cadherin by a variety of transcriptional factors, including Twist1, Snail, Slug, SIP1, Zeb1 and E47. However, during metastatic evolution, the interplay between different EMT inducers has been investigated limitedly. Previously study demonstrated that hypoxia induces EMT of HNSCC through induction of Twist1 expression. Additionally showed that Twist1 promotes EMT and tumor-initiating capability through upregulation of Bmi1, and co-expression Twist1 and Bmi1 predicts a worse prognosis of HNSCC cases. Accumulated evidence suggests that microRNAs play essential roles in cancer progression and metastasis. Therefore, we aim to investigate the role of microRNA in Twist1-mediated cancer metastasis, and the interplay between Twist1 and other EMT regulators. Our preliminary data showed that the expression of miR-29 family, including miR-29a, b, and c were increased in Twist1-overexpressing HNSCC cells. Furthermore, we discovered that SIN3A, a co-repressor of another EMT regulator Snail, is a target of miR-29s. We therefore speculate that Twist1 modifies the function of Snail through microRNA machinery. In this proposal, we will delineate the regulatory mechanism of the Twist1-miR29s-SIN3A axis. We will also investigate the molecular interplay between Twist1 and Snail through Twist1-miR29s-SIN3A signal pathway. Furthermore, we will elucidate the molecular basis and pathophysiologic significance of Twist1-Snail interaction under hypoxic environment. Finally, we will confirm the in vitro finding by in vivo animal study and HNSCC samples. These results will provide crucial information for understanding the molecular basis of HNSCC metastasis, and will be valuable for developing new therapeutic strategies against advanced HNSCC.

Official Title
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Observational Study on the Investigation of the Molecular Mechanism and Clinical Significance of the Interplay Between Twist1 and Other EMT Regulators Through microRNA-29 Family.

Conditions
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Head-and-Neck Squamous Cell Carcinoma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Head and neck cancer Exclusion Criteria: pregnant woman

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Head and neck cancer<br>Subjects who suffer from oral cancer. Collect a 0.5x0.5Cm2 tissue sample of the tumor during the surgery. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The interplay between Twist1 and other EMT regulators throigh microRNA-29 family |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head-and-Neck squamous cell carcinoma (HNSCC), epithelial-mesenchymal transition (EMT), microRNA29, Twist1