MYB/LINC00092 regulatory axis promotes the progression of papillary thyroid carcinoma.

Abstract

Introduction: Thyroid carcinoma is the most frequent malignancy in different endocrine-related tumours. In this study, we demonstrated a long non-coding RNA LINC00092-associated molecular mechanism in promoting the progression of papillary thyroid carcinoma (PTC).

Material and methods: The expression of LINC00092 was analysed in the The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) patient cohorts and further determined by q-PCR. (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) (MTT) assay, and wound healing assay confirmed the function of LINC00092 in migration and proliferation. Q-ChIP validated the transcriptional target. Luciferase reporter assay validated the miRNA-mRNA target.

Results: The analysis in patient cohorts and in PTC TPC-1 cells showed that the expression of LINC00092 was repressed in thyroid carcinoma. In addition, the expression of LINC00092 was negatively associated with the advanced thyroid TNM stages. LINC00092 repressed epithelial-mesenchymal transition (EMT), migration, and proliferation of TPC-1 cells. Interestingly, we identified that MYB, a well-studied tumour promoter, is a transcription factor of LINC00092, thereby the expression of LINC00092 was directly repressed by MYB. Furthermore, miR-4741 was also validated as a direct target of MYB and was induced by MYB. Notably, LINC00092 was repressed by miR-4741 through the direct 3'-untranslational region (3'-UTR) target. Therefore, MYB induced EMT of TPC-1 cells by repressing LINC00092 directly or indirectly via miR-4741.

Conclusions: Our study validated that LINC00092 is a tumour suppressor lncRNA in PTC. MYB directly or indirectly represses LINC00092, which contributes to the PTC progression. MYB, LINC00092, and miR-4741 form a coherent feed forward loop. The axis of MYB-LINC00092 promotes progression of PTC.