Selenomethionine Suppress the Progression of Poorly Differentiated Thyroid Cancer via LncRNA NONMMUT014201/miR-6963-5p/Srprb Pathway

Rongfang Pan; Junyu Zhao; Jinming Yao; Yanyan Gao; Lin Liao

doi:10.2174/0113862073286006231228070738

Selenomethionine Suppress the Progression of Poorly Differentiated Thyroid Cancer via LncRNA NONMMUT014201/miR-6963-5p/Srprb Pathway

Comb Chem High Throughput Screen. 2024 Jan 1. doi: 10.2174/0113862073286006231228070738. Online ahead of print.

Authors

Rongfang Pan¹, Junyu Zhao², Jinming Yao², Yanyan Gao³, Lin Liao¹

Affiliations

¹ Department of Endocrinology and Metabology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, China.
² Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Institute of Nephrology, Jinan 250014, Shandong, China.
³ Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China.

PMID: 38173060
DOI: 10.2174/0113862073286006231228070738

Abstract

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.

Methods: 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.

Results: 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.

Keywords: LncRNA NONMMUT014201; Srprb.; miR-6963-5p; poorly differentiated thyroid cancer; selenomethionine.