Table_1_The Role of LINC00284 in the Development of Thyroid Cancer via Its Regulation of the MicroRNA-30d-5p-Mediated ADAM12/Notch Axis.doc

Thyroid cancer is a commonly diagnosed endocrine malignancy with increasing incidence worldwide. Long noncoding RNAs (lncRNAs) are known to function in the invasion and metastasis of thyroid cancer. According to the GSE66783 microarray dataset, long intergenic nonprotein coding RNA 284 (LINC00284) is aberrantly upregulated in thyroid cancer tissues. However, information regarding the specific role of LINC00284 in thyroid cancer remains elusive. Therefore, the current study set out to determine the role of LINC00284 in the development of thyroid cancer, along with an investigation of the underlying molecular mechanism. In parallel with the microarray data from GSE66783, LINC00284 was observed to be expressed at high levels in thyroid cancer cell lines. Moreover, loss-of-function experiments revealed that the downregulation of LINC00284 reduced aldehyde dehydrogenase (ALDH) activity and thyroid cancer cell proliferation, colony formation, and invasiveness, which promoted cell apoptosis. Mechanistically, using dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays, LINC00284 was identified to competitively bind to microRNA-30d-5p (miR-30d-5p), which was observed to be expressed at low levels in thyroid cancer tissues and cells and directly targets the oncogene a disintegrin and metalloproteinase 12 (ADAM12). Overexpression of miR-30d-5p exerted tumor-suppressive effects on the malignant activity of thyroid cancer cells, changes that were reversed by LINC00284 overexpression or ADAM12 overexpression. Furthermore, LINC00284 activated the Notch signaling pathway by competitively binding to miR-30d-5p and increasing the expression of ADAM12. Finally, by performing in vivo experiments, we found that LINC00284 silencing or miR-30d-5p overexpression suppressed the tumorigenic ability of thyroid cancer cells and that overexpression of miR-30d-5p inhibited the LINC00284-induced tumorigenesis of thyroid cancer cells. Collectively, our findings indicate that LINC00284 competitively binds to miR-30d-5p and activates the ADAM12-dependent Notch signaling pathway, thereby promoting the development of thyroid cancer.</p