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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Reduced USP39 expression inhibits malignant proliferation of medullary thyroid carcinoma in vitro
Yong An1, Shuwen Yang1, Kai Guo1
1Department of Head & Neck Surgery, Fudan University Shanghai Cancer Center and Department of Oncology, Shanghai Medical College, Fudan University, 6W of No.3 Building, No.270 DongAn Road, Shanghai, 200223, China.
Background:
Medullary thyroid carcinoma (MTC) constitutes approximately 5 % of all thyroid cancers and carries a worse prognosis than other differentiated thyroid cancers. Targeted therapies are being investigated for systemic treatment of MTC. Ubiquitin-specific peptidase 39 (USP39) functions in pre-mRNA splicing as a component of the U4/U6-U5 tri-snRNP and also participates in spindle checkpoint and cytokinesis. In this study, we aimed to evaluate the potential role in MTC.
Methods:
We used lentivirus-delivered short hairpin RNA (shRNA) to silence USP39 expression in one MTC cell line TT. USP39 expression was detected by qPCR and Western blot. For functional analysis, MTT assay was performed to evaluate the proliferation activity, and FACS was used to assess the cell distribution in the cell cycle. Moreover, the expressions of cell cycle-related proteins were examined by Western blot.
Results:
Both two shRNA sequences against USP39 could efficiently reduce its expression in TT cells. Knockdown of USP39 significantly decreased cell proliferation and caused cell cycle arrest at G2/M phase. Moreover, G2/M phase-associated proteins, Cyclin B1 and CDK1, were obviously down-regulated in TT cells after USP39 silencing.
Conclusions:
Therefore, knockdown of USP39 is likely to provide a novel alternative to targeted therapy of MTC and deserves further investigation.
Insights
Targeting Ubiquitin-specific peptidase 39 (USP39) in medullary thyroid carcinoma (MTC) significantly inhibits cancer cell proliferation and induces cell cycle arrest. USP39 knockdown presents a potential new therapeutic strategy for MTC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Medullary thyroid carcinoma (MTC) is a rare thyroid cancer with a poor prognosis.
- Targeted therapies are under investigation for MTC treatment.
- Ubiquitin-specific peptidase 39 (USP39) plays roles in pre-mRNA splicing and cell division.
Purpose of the Study:
- To investigate the role of USP39 in medullary thyroid carcinoma.
- To evaluate USP39 as a potential therapeutic target for MTC.
Main Methods:
- USP39 expression was silenced in MTC cells (TT cell line) using lentivirus-delivered short hairpin RNA (shRNA).
- Cell proliferation was assessed using MTT assays.
- Cell cycle distribution and related protein expression (Cyclin B1, CDK1) were analyzed by FACS and Western blot.
Main Results:
- USP39 knockdown effectively reduced USP39 expression in MTC cells.
- Silencing USP39 significantly inhibited cell proliferation.
- USP39 knockdown led to G2/M phase cell cycle arrest and down-regulation of Cyclin B1 and CDK1.
Conclusions:
- USP39 plays a critical role in MTC cell proliferation and cell cycle progression.
- Targeting USP39 demonstrates potential as a novel therapeutic strategy for medullary thyroid carcinoma.
- Further research into USP39 inhibition for MTC treatment is warranted.
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