background:
Poorly differentiated thyroid cancer (PDTC) is a special type of thyroid
cancer that threatens the life of the patients. Unfortunately, there are no effective treatments for
PDTC right now, so it is urgent to search for new efficacious drugs. This experiment was designed
to elucidate the effects of selenomethionine (SeMet) on PDTC in vitro and vivo.
method:
A xenograft animal model was used to assay the volume and weight of PDTC. LncRNA
NOMMMUT014201 expression was detected by fluorescence in situ hybridization and Real-time
quantitative PCR (qRT-PCR). In vitro experiments were carried on in WRO cells. The Cell Counting
Kit-8 assay was performed to test the effect of SeMet on the proliferation of cells. And the migration
and invasion of WRO cells by the wound-healing assay, Transwell migration and invasion
assays. The cell apoptosis was measured by flow cytometry. In addition, genes related to proliferation,
migration, invasion and apoptosis were detected through qRT-PCR and Western Blot.
result:
SeMet inhibited the proliferation, migration and invasion and promoted the apoptosis of
WRO cells in a dose-dependent manner. Then vivo, SeMet significantly suppressed the volume
and weight of PDTC. And SeMet downregulated the expressions of Ki67, PCNA, MMP2,
MMP9 and BCL2, but upregulated that of BAX and Cleaved-Caspase 3. Moreover, SeMet upregulated
the level of LncRNA NOMMMUT014201 both vivo and in vitro. In addition, repression
of LncRNA NOMMMUT014201 removed the inhibition effect of SeMet on WRO cell
growth significantly (p<0.05). Further investigation showed that LncRNA NOMMMUT014201
downregulated the expression of miR-6963-5p in PDTC cells, but miR-6963-5p inhibited the
level of Srprb. In addition, sh-LncRNA NOMMMUT014201 enhanced the proliferation, migration
and invasion but inhibited the apoptosis of WRO cells. However, inhibited miR-6963-5p or
overexpressed Srprb relieved the effects of sh-LncRNA NOMMMUT014201on WRO cells.
conclusion:
Collectively, SeMet inhibits the growth of PDTC in a dose-dependent manner
through LncRNA NONMMUT014201/miR-6963-5p/Srprb signal pathway, thus suggesting that
SeMet might be a potential drug for PDTC treatment.