This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Xiaofeng Tian
Second Hospital of Dalian Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-3034-0634
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
The BRAF V600E mutation is closely associated with aggressive clinicopathologic features and increased recurrence and disease-specific mortality of papillary thyroid cancer (PTC). Silent mating type information regulation 2 homolog-1 (SIRT1) has long been suggested to have tumor promotor activity and is strongly associated with the presence of BRAF mutations and higher grades of malignancy in many cancer types. However, no evidence or mechanism have been identified in PTC.
Methods
PTC tissue samples and their adjacent normal tissues from 42 PTC patients were collected; qRT-PCR, western blotting, T1799A BRAF mutation testing were utilized and the association with clinicopathologic features were assessed. Three different thyroid cell lines, Nthy-ori 3 − 1, TPC-1 and BCPAP, were used in in vitro studies. Cell counting kits and cell cycle analyses were utilized to investigate the level of cell proliferation and cell cycle progression. Transwell and Matrigel invasion assays were used to investigate the level of cell migration and invasion.
Results
SIRT1 is significantly upregulated in PTC, especially in lymph node metastatic and BRAF V600E-mutated patients. Cell counting kits and cell cycle analyses demonstrated that SIRT1 significantly promoted cell proliferation and cell cycle progression in BRAF V600E-mutated cells. Transwell and Matrigel invasion assays confirmed that SIRT1 promoted the migration and invasion ability of BRAF V600E-mutated cells. Additionally, the results of western blotting showed that the aberrant activation of the mitogen-activated protein kinase (MAPK) pathway played a crucial role in the tumor-promoting role of SIRT1 in BRAF V600E-mutated PTC biology.
Conclusions
SIRT1 expression with a BRAF V600E mutation may serve as new candidate targets for the diagnosis and treatment of papillary thyroid carcinomas.
Keywords
papillary thyroid cancer; BRAF V600E mutation; SIRT1; metastasis; MAPK
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Xiaofeng Tian
Second Hospital of Dalian Medical University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-3034-0634
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 13 May, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
The BRAF V600E mutation is closely associated with aggressive clinicopathologic features and increased recurrence and disease-specific mortality of papillary thyroid cancer (PTC). Silent mating type information regulation 2 homolog-1 (SIRT1) has long been suggested to have tumor promotor activity and is strongly associated with the presence of BRAF mutations and higher grades of malignancy in many cancer types. However, no evidence or mechanism have been identified in PTC.
Methods
PTC tissue samples and their adjacent normal tissues from 42 PTC patients were collected; qRT-PCR, western blotting, T1799A BRAF mutation testing were utilized and the association with clinicopathologic features were assessed. Three different thyroid cell lines, Nthy-ori 3 − 1, TPC-1 and BCPAP, were used in in vitro studies. Cell counting kits and cell cycle analyses were utilized to investigate the level of cell proliferation and cell cycle progression. Transwell and Matrigel invasion assays were used to investigate the level of cell migration and invasion.
Results
SIRT1 is significantly upregulated in PTC, especially in lymph node metastatic and BRAF V600E-mutated patients. Cell counting kits and cell cycle analyses demonstrated that SIRT1 significantly promoted cell proliferation and cell cycle progression in BRAF V600E-mutated cells. Transwell and Matrigel invasion assays confirmed that SIRT1 promoted the migration and invasion ability of BRAF V600E-mutated cells. Additionally, the results of western blotting showed that the aberrant activation of the mitogen-activated protein kinase (MAPK) pathway played a crucial role in the tumor-promoting role of SIRT1 in BRAF V600E-mutated PTC biology.
Conclusions
SIRT1 expression with a BRAF V600E mutation may serve as new candidate targets for the diagnosis and treatment of papillary thyroid carcinomas.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
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