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GABPA inhibits inva...
GABPA inhibits invasion/metastasis in papillary thyroid carcinoma by regulating DICER1 expression
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- Yuan, Xiaotian (författare)
- Karolinska Institute,Shandong University,Karolinska University Hospital
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- Mu, Ninni (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Wang, Na (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Strååt, Klas (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Sofiadis, Anastasios (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Guo, Yanxia (författare)
- Karolinska Institute,Karolinska University Hospital,Shandong University
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- Stenman, Adam (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Li, Kailin (författare)
- Shandong University
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- Cheng, Guanghui (författare)
- Shandong University
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- Zhang, Lu (författare)
- Shandong University
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- Kong, Feng (författare)
- Shandong University
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- Ekblad, Lars (författare)
- Lund University,Lunds universitet,Huvud- och halscancergruppen,Forskargrupper vid Lunds universitet,Head and Neck Cancer Research Group,Lund University Research Groups
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- Wennerberg, Johan (författare)
- Lund University,Lunds universitet,Öron-, näs- och halssjukdomar, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Otorhinolaryngology (Lund),Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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- Nilsson, Inga Lena (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Juhlin, C. Christofer (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Larsson, Catharina (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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- Xu, Dawei (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska University Hospital
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(creator_code:org_t)
- 2018-09-04
- 2019
- Engelska.
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 38:7, s. 965-979
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- The ETS family transcription factor GABPA is suggested as an oncogenic element, which is further supported by the recent reporting of it as the sole ETS member to activate the mutant TERT promoter in thyroid carcinomas (TC). However, it remains unclear how GABPA contributes to TC pathogenesis. The present study is designed to address this issue. TERT expression was significantly diminished in TERT promoter-mutated TC cells upon GABPA inhibition. Surprisingly, GABPA depletion led to robustly increased cellular invasion independently of TERT promoter mutations and TERT expression. DICER1, a component of the microRNA machinery, was identified as a downstream effector of GABPA. GABPA facilitated Dicer1 transcription while its depletion reduced Dicer1 expression. The mutation of the GABPA binding site in the DICER1 promoter led to diminished basal levels of DICER1 promoter activity and abolishment of GABPA-stimulated promoter activity as well. The forced DICER1 expression abrogated the invasiveness of GABPA-depleted TC cells. Consistently, the analyses of 93 patients with papillary thyroid carcinoma (PTC) revealed a positive correlation between GABPA and DICER1 expression. GABPA expression was negatively associated with TERT expression and promoter mutations, in contrast to published observations in cancer cell lines. Lower GABPA expression was associated with distant metastasis and shorter overall/disease-free survival in PTC patients. Similar results were obtained for PTC cases in the TCGA dataset. In addition, a positive correlation between GABPA and DICER1 expression was seen in multiple types of malignancies. Taken together, despite its stimulatory effect on the mutant TERT promoter and telomerase activation, GABPA may itself act as a tumor suppressor rather than an oncogenic factor to inhibit invasion/metastasis in TCs and be a useful predictor for patient outcomes.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
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Oncogene
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Till lärosätets databas
- Av författaren/redakt...
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Yuan, Xiaotian
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Mu, Ninni
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Wang, Na
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Strååt, Klas
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Sofiadis, Anasta ...
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Guo, Yanxia
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visa fler...
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Stenman, Adam
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Li, Kailin
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Cheng, Guanghui
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Zhang, Lu
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Kong, Feng
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Ekblad, Lars
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Wennerberg, Joha ...
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Nilsson, Inga Le ...
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Juhlin, C. Chris ...
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Larsson, Cathari ...
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Xu, Dawei
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Medicinsk geneti ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
- Artiklar i publikationen
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Oncogene
- Av lärosätet
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Lunds universitet
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Karolinska Institutet