miRNA-106a directly targeting RARB associates with the expression of Na+/I− symporter in thyroid cancer by regulating MAPK signaling pathway

Abstract

BackgroundSerum miRNAs profiles between papillary thyroid carcinoma (PTC) patients with non-131I and 131I-avid lung metastases are differentially expressed. These miRNAs have to be further validated and the role of these miRNAs in the molecular function level of thyroid cancer cell lines has not been investigated.MethodsExpression levels of six identified miRNAs were assessed via quantitative real-time PCR (qRT-PCR) in the serum of eligible patients. Dual-luciferase reporter assay was used to determine the potential target of miR-106a. Cell viability and apoptosis were evaluated by MTT assay and flow cytometry analysis, respectively. The change of gene expression was detected by qRT-PCR and western blotting analysis. In vitro iodine uptake assay was conducted by a γ-counter.ResultsCompared to PTC patients with 131I-avid lung metastases, miR-106a was up-regulated in the serum of patients with non-131I-avid lung metastases. The results of dual-luciferase reporter assay demonstrated that miR-106a directly targeted retinoic acid receptor beta (RARB) 3′-UTR. miR-106a-RARB promoted viability of thyroid cancer cells by regulating MEKK2-ERK1/2 and MEKK2-ERK5 pathway. miR-106a-RARB inhibited apoptosis of thyroid cancer cells by regulating ASK1-p38 pathway. Moreover, miR-106a-RARB could regulate the expression of sodium iodide symporter, TSH receptor and alter the iodine uptake function of thyroid cancer cells.ConclusionsmiRNA-106a, directly targeting RARB, associates with the viability, apoptosis, differentiation and the iodine uptake function of thyroid cancer cell lines by regulating MAPK signaling pathway in vitro. These findings in the present study may provide new strategies for the diagnosis and treatment in radioiodine-refractory differentiated thyroid carcinoma.

Interplay of TGFβ signaling and microRNA in thyroid cell loss of differentiation and cancer progression

“…In addition, miRNA could also regulate thyroid differentiation in an indirect manner. For example, miR-106a is upregulated in the serum of patients who have thyroid-cancer metastases in the lung that are not avid for radioiodine (25). Similarly, miR-106a regulates the expression of retinoic acid receptor beta, (RARβ) which influences thyroid cells' differentiation.…”

“…The overexpression of miR-106a in the PTC cell line increases cell viability and invasion but reduces apoptosis; the opposite occurs when inhibiting miR-106a in ATC cell lines. Moreover, targeting miR-106a with antagomir increases the expression of NIS and TSHR while sensitizing ATC cells to radioiodine treatment (25). Interestingly, miR-146b regulates the expression of RARβ (26) and serum miR-146b levels are also associated with thyroid tumors poor prognosis (27).…”

Solute carrier family 35 member F2 is indispensable for papillary thyroid carcinoma progression through activation of transforming growth factor‐β type I receptor/apoptosis signal‐regulating kinase 1/mitogen‐activated protein kinase signaling axis

“…H, Sections of xenograft tumor tissues stained with HE as well as IHC staining for SLC35F2 and Ki-67 (**P < .01, ***P < .001) HE ET AL.| 653 the thyroid carcinogenesis, transmits growth signals from the plasma membrane to the nucleus and plays a central part in promoting cancer cell proliferation and survival [37][38][39]. Shen et al report that miRNA-106a directly targeting RARB influence the viability, apoptosis, differentiation of PTC, and alter the iodine uptake function by regulating MAPK pathway 40. Here, we unravel for the first time thatSLC35F2 exerts its oncogenic effect on PTC progression mainly through the MAPK pathway, with dependence on the induction and activation of TGFBR-1 and ASK-1.…”

High-throughput small RNA and transcriptome sequencing reveal reproduction-related microRNAs and mRNA in ovary of Geese in Counter-Season Production

“…In the current study, these genes were significantly lower expressed in the atrophic ovaries. In addition, retinoic acid receptor beta (RARB), associates with the viability, apoptosis, differentiation and the iodine uptake function of cancer cell lines by regulating MAPK signaling pathway [31]. RB transcriptional corepressor like 1 (RBL1) mainly plays an important role in the context of G1-S transition and as an apoptotic trigger [32].…”