ABSTRACT
As a tumor-associated biological molecule, microRNA-143-3p (miR-143-3p) is implicated in the progression of papillary thyroid carcinoma (PTC). We conducted this study to elucidate the effects of miR-143-3p mediated by Musashi RNA binding protein 2 (MSI2) on the biological activities of PTC cells. The K1 cells with the lowest miR-143-3p expression were selected for the experiments. The targeting relationship between miR-143-3p and MSI2 was verified. The biological functions of miR-143-3p and MSI2 with respect to K1 cell proliferation, cycle distribution, apoptosis, invasion, migration, and tumorigenesis were studied using gain- and loss-of-function assays both in vitro and in vivo. MSI2 was verified to be a target gene of miR-143-3p. Cells treated with upregulation of miR-143-3p or silencing of MSI2 exhibited significantly decreased the expression of Bcl-2, PCNA, MCM2, Ki67, MSI2, MMP-2, and MMP-9. This was accompanied by inhibited cell proliferation, cell invasion, and migration, as well as a significant increase in Bax expression, cell cycle arrest, and cell apoptosis. More importantly, the tumor inhibitory effects of upregulated miR-143-3p were also confirmed in the tumor xenografts in nude mice. Our results indicate that upregulation of miR-143-3p suppresses the progression of PTC by impeding cell growth, invasion, and migration via downregulation of MSI2, highlighting the potential of miR-143-3p as a target for future PTC treatment.
Subject(s)
Cell Proliferation/genetics , MicroRNAs/genetics , RNA-Binding Proteins/genetics , Thyroid Cancer, Papillary/genetics , Animals , Apoptosis , Cell Cycle/genetics , Cell Line, Tumor , Cell Movement/genetics , Female , Gene Expression Regulation, Neoplastic , Heterografts , Humans , Male , Mice , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Prognosis , Thyroid Cancer, Papillary/pathology , Transcriptional Activation/geneticsABSTRACT
Thyroid cancer (TC) is an endocrine malignancy with rising incidence. Long non-coding RNAs (lncRNAs) can serve as diagnostic and prognostic biomarkers for TC. Thus, we studied roles of LINC01296 in TC progression. Initially, the Gene Expression Omnibus (GEO) database was used to detect the differentially expressed genes in human TC samples and the potential mechanism. Expression of LINC01296 and miR-143-3p in TC tissues and cells was measured. The transfection of TC cells was conducted with si-LINC01296, si-Musashi 2 (MSI2), mimic or inhibitor of miR-143-3p to determine their effects on TC cell proliferation, migration, invasion, apoptosis and the AKT/STAT3 signaling pathway. Finally, in vivo assay was performed to verify role of miR-143-3p in tumorigenesis of TC cells in nude mice. LINC01296 was predicted to bind to miR-143-3p to modulate MSI2 expression, thus regulating the occurrence and development of TC. LINC01296 was up-regulated, while miR-143-3p was down-regulated in TC cells and tissues. LNC01296 specifically bound to miR-143-3p and MSI2 was a target of miR-143-3p. Besides, LINC01296 silencing or miR-143-3p overexpression inhibited migration, invasion, proliferation and advanced apoptosis of TC cells. Additionally, silenced LINC01296 or overexpressed miR-143-3p reduced phosphorylated STAT3/STAT3, phosphorylated AKT/AKT, B-cell lymphoma-2 (Bcl-2) and CyclinD1 levels but elevated BCL2-associated X (Bax), Cleaved Caspase3 and Caspase3 levels. Also, tumorigenesis of TC cells in nude mice was inhibited with the silencing of LINC01296. In summary, LINC01296/miR-143-3p/MSI2 axis regulated development of TC through the AKT/STAT3 signaling pathway.
