Abstract

BackgroundMedullary 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.MethodsWe 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.ResultsBoth 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.ConclusionsTherefore, knockdown of USP39 is likely to provide a novel alternative to targeted therapy of MTC and deserves further investigation.

Highlights

  • Medullary thyroid carcinoma (MTC) constitutes approximately 5 % of all thyroid cancers and carries a worse prognosis than other differentiated thyroid cancers

  • Knockdown of Ubiquitin-specific peptidase 39 (USP39) expression with lentivirus-delivered short hairpin RNA (shRNA) TT cells were transduced with shRNA-expressing lentivirus (shCon or shUSP39(S1)/(S2))

  • The inhibitory effect of USP39 shRNA on its endogenous expression in TT cells was examined by qRT-PCR and Western blotting

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Summary

Introduction

Medullary thyroid carcinoma (MTC) constitutes approximately 5 % of all thyroid cancers and carries a worse prognosis than other differentiated thyroid cancers. Ubiquitin-specific peptidase 39 (USP39) functions in pre-mRNA splicing as a component of the U4/U6-U5 tri-snRNP and participates in spindle checkpoint and cytokinesis. Medullary thyroid carcinoma (MTC) accounts for 5–10 % of all thyroid cancers and carries a worse prognosis than other differentiated thyroid cancers with an overall 10-year survival rate of 75–85 % [1, 2]. Hereditary MTC can present in isolation (familial medullary thyroid cancer (FMTC)) or as part. USP39 does not have ubiquitin-specific peptidase activity but plays an essential role in pre-mRNA splicing as a component of the U4/U6-U5 tri-snRNP, one of the building blocks of the

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