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《生物化学与生物物理学报：英文版》
>MicroRNA-99a-3p/GRP94 axis affects metastatic progression of human papillary thyroid carcinoma by regulating ITGA2 expression and localization
MicroRNA-99a-3p/GRP94 axis affects metastatic progression of human papillary thyroid carcinoma by regulating ITGA2 expression and localization
Papillary thyroid cancer (PTC) usually has favorable prognosis;however,distant metastasis is a leading cause of death associated with PTC.MicroRNA-99a-3p (miR-99a-3p) is a member of the miR-99 family that is shown to be a tumor suppressor in various human cancers including the anaplastic thyroid cancer,another type of thyroid cancer.The Cancer Genome Atlas database and our previous study reported that miR-99a-3p is downregulated in human PTC tissues as well as human papillary thyroid carcinoma B-CPAP and TPC-1 cell lines.However,its pathological role in PTC remains unclear,especially its impact on PTC metastasis.In the present study,the role of miR-99a-3p in PTC metastasis was molecularly evaluated in in vitro and in vivo models.Our functional study revealed that overexpressing miR-99a-3p significantly suppresses epithelial-mesenchymal transition (EMT) and anoikis resistance as well as migration and invasion of B-CPAP and TPC-1 cells.The mechanical study indicated that glucose-regulated protein 94 (GRP94) is the direct target of miR-99a-3p.Moreover,GRP94 overexpression reverses the inhibitory effect of miR-99a-3p on PTC metastasis.In addition,the miR-99a-3p/GRP94 axis exerts its effect via inhibiting the expression and cytoplasmic relocation of integrin 2α (ITGA2).Furthermore,in vivo experiments confirmed that miR-99a-3p significantly inhibits tumor growth and lung metastasis in PTC xenograft mice.Overall,our findings suggested that the miR-99a-3p/GRP94/ITGA2 axis may be a novel therapeutic target for the prevention of PTC metastasis.
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