Study on the Interplay Between Twist1 and Other EMT Regulators Through microRNA-29 Family.
NCT ID: NCT01927354
Last Updated: 2013-09-16
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
UNKNOWN
Total Enrollment
100 participants
Study Classification
OBSERVATIONAL
Study Start Date
2012-12-31
Study Completion Date
2014-03-31
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.
Conditions
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Head-and-Neck Squamous Cell Carcinoma
Keywords
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Head-and-Neck squamous cell carcinoma (HNSCC)
epithelial-mesenchymal transition (EMT)
microRNA29
Twist1
Study Design
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Observational Model Type
COHORT
Study Groups
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Head and neck cancer
Subjects who suffer from oral cancer. Collect a 0.5x0.5Cm2 tissue sample of the tumor during the surgery.
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
* Head and neck cancer
Exclusion Criteria
* pregnant woman
Minimum Eligible Age
20 Years
Maximum Eligible Age
80 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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National Taiwan University Hospital
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Shin-Jung Cheng, DDS, MS, PhD
Role: PRINCIPAL_INVESTIGATOR
Locations
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National Taiwan University Hospital research Ethics Committee
Taipei, , Taiwan
Site Status
RECRUITING
Countries
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Taiwan
Central Contacts
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Facility Contacts
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Shin-Jung Cheng, DDS, MS, PhD
Role: primary
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RESULT
Yang MH, Hsu DS, Wang HW, Wang HJ, Lan HY, Yang WH, Huang CH, Kao SY, Tzeng CH, Tai SK, Chang SY, Lee OK, Wu KJ. Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition. Nat Cell Biol. 2010 Oct;12(10):982-92. doi: 10.1038/ncb2099. Epub 2010 Sep 5.
Reference Type
RESULT
Yang MH, Wu KJ. TWIST activation by hypoxia inducible factor-1 (HIF-1): implications in metastasis and development. Cell Cycle. 2008 Jul 15;7(14):2090-6. doi: 10.4161/cc.7.14.6324. Epub 2008 May 21.
Reference Type
RESULT
Yang MH, Wu MZ, Chiou SH, Chen PM, Chang SY, Liu CJ, Teng SC, Wu KJ. Direct regulation of TWIST by HIF-1alpha promotes metastasis. Nat Cell Biol. 2008 Mar;10(3):295-305. doi: 10.1038/ncb1691. Epub 2008 Feb 24.
Reference Type
RESULT
Other Identifiers
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201112085RID
Identifier Type: -
Identifier Source: org_study_id