Dataset Information

MicroRNA-203a-3p may prevent the development of thyroid papillary carcinoma via repressing MAP3K1 and activating autophagy.

ABSTRACT:

Background

Papillary thyroid carcinoma (PTC) grows slowly but has a great risk of metastasis. MicroRNAs are well known as vital tumor-related gene regulators. In PTC, the role of miR-203a-3p and the underlying mechanisms remain not completely understood.

Methods

We conducted CCK8 assay, wound healing assay, transwell experiment and flow cytometry analyses to investigate the function of miRNA-203a-3p. The interaction of miRNA-203a-3p with its gene MAP3K1 was characterized by quantitative real-time polymerase chain reaction, western blotting and luciferase assay.

Results

We found that the levels of miRNA-203a-3p were statistically decreased in PTC tissues. When mimics were delivered to TPC-1 and KTC-1 cells to upregulate miR-203a-3p, it was observed that cell proliferation, metastatic abilities and cell cycle process were prevented but cell apoptosis was enhanced. Furthermore, we proved the interaction between MAP3K1 and miR-203a-3p. Intriguingly, similar to miR-203a-3p mimics, siMAP3K1 showed a tumor-suppressive effect, and this effect could be reversed when miR-203a-3p was simultaneously inhibited. Finally, selected autophagy-linked proteins such as LC3 Beclin-1 were detected and found to be increased when miR-203a-3p was upregulated or MAP3K1 was inhibited.

Conclusion

Overall, miR-203a-3p inhibits the oncogenic characteristics of TPC-1 and KTC-1 cells via suppressing MAP3K1 and activating autophagy. Our findings might enrich the understanding and the therapeutic strategies of PTC.

SUBMITTER: Dai L

PROVIDER: S-EPMC9169216 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

MicroRNA-203a-3p may prevent the development of thyroid papillary carcinoma via repressing MAP3K1 and activating autophagy.

Dai Lei L Zhang Weidong W Wu Xianjiang X Zhou Shuihong S

Journal of clinical laboratory analysis 20220506 6

<h4>Background</h4>Papillary thyroid carcinoma (PTC) grows slowly but has a great risk of metastasis. MicroRNAs are well known as vital tumor-related gene regulators. In PTC, the role of miR-203a-3p and the underlying mechanisms remain not completely understood.<h4>Methods</h4>We conducted CCK8 assay, wound healing assay, transwell experiment and flow cytometry analyses to investigate the function of miRNA-203a-3p. The interaction of miRNA-203a-3p with its gene MAP3K1 was characterized by quanti ...[more]

PMID: 35524422

Similar Datasets

Project description:Background Thyroid cancer is the most common malignant tumor in the endocrine system. Papillary thyroid carcinoma (PTC) accounts for the vast majority of cases in this cancer. Recently, the vital role of circular RNA (circRNA) has been acknowledged in various cancers, and this study aimed to investigate the role of circ_0058124 and related mechanism of its action in PTC. Materials and Methods The expression of circ_0058124, miR-370-3p and LIM domain only (LMO4) was detected by qRT-PCR in tissue samples (PTC tissues or normal tissues, n=20) and cell lines (non-cancer cell line, Nthy-ori 3–1, and PTC cell lines, IHH-4 and TPC-1). For functional analysis, cell proliferation was investigated using CCK-8 assay and colony formation assay. Cell migration and invasion were determined using transwell assay, and cell migration was also assessed by wound healing assay. Cell apoptosis was monitored by flow cytometry assay. For mechanism analysis, the interaction between miR-370-3p and circ_0058124 or LMO4 predicted by the bioinformatics analysis was validated by dual-luciferase reporter assay or RIP assay. The effect of circ_0058124 on tumor growth in vivo was identified by establishing the Xenograft model. Results The expression of circ_0058124 was enhanced in PTC tissues and cells. Circ_0058124 knockdown inhibited viability, colony formation, migration and invasion and promoted apoptosis of PTC cells. Besides, circ_0058124 knockdown also blocked tumor growth in vivo. miR-370-3p was a target of circ_0058124, and circ_0058124 regulated the expression of LMO4, a target of miR-370-3p, by targeting miR-370-3p. Rescue experiments presented that miR-370-3p inhibition reversed the inhibitory effects of circ_0058124 knockdown on PTC development, and LMO4 overexpression reversed the effect of miR-370-3p restoration on PTC development. Conclusion Circ_0058124 promoted the development of PTC by mediating the miR-370-3p/LMO4 axis, and circ_0058124, functioned as an oncogene in PTC, might be used as a promising biomarker for PTC diagnosis and treatment.

Project description:Background: MiR-146b has been reported to be overexpressed in papillary thyroid cancer (PTC) tissues and associated with aggressive PTC. MiR-146b is regarded as a relevant diagnostic marker for this type of cancer. MiR-146b-5p has been confirmed to increase cell proliferation by repressing SMAD4. However, detailed functional analysis of another mature form of miR-146b, miR-146b-3p, has not been carried out. This study aimed to identify the differential expression of miR-146b-5p and miR-146b-3p in more aggressive PTC associated with lymph node metastasis, and further elucidate the contribution and mechanism of miR-146b-3p in the process of PTC metastasis. Methods: Expression of miR-146b-5p and miR-146b-3p was assessed in formalin-fixed paraffin-embedded tissue samples from PTC patients, and the relationship with lymph node metastasis was analyzed. A variety of PTC cells, including BHP10-3, BHP10-3SCmice, and K1 cells, were cultured and treated with miR-146b-5p or miR-146b-3p mimics/inhibitors. The cell migration and invasion abilities were characterized by the real-time cell analyzer assay and Transwell™ assay. PTC xenograft models were used to examine the effect of miR-146b-3p on PTC metastatic ability in vivo. Direct downstream targets of miR-146b-3p were analyzed by luciferase reporter assay and Western blotting. The mechanism by which miR-146b-3p affects cell metastasis was further characterized by co-transfection with merlin, the protein product of the NF2 gene. Results: MiR-146b-5p and miR-146b-3p expression was significantly higher in thyroid cancer tissues and cell lines than in normal thyroid tissue and cells. Moreover, expression of miR-146b-5p and miR-146b-3p was further increased in thyroid metastatic nodes than in thyroid cancer. After overexpression of miR-146b-5p or miR-146b-3p in BHP10-3 or K1 cells, PTC migration and invasion were increased. Notably, miR-146b-3p increased cell migration and invasion more obviously than did miR-146b-5p. Overexpression of miR-146b-3p also significantly promoted PTC tumor metastasis in vivo. Luciferase reporter assay results revealed that NF2 is a downstream target of miR-146b-3p in PTC cells, as miR-146b-3p bound directly to the 3' untranslated region of NF2, thus reducing protein levels of NF2. Overexpression of merlin reversed the enhanced aggressive effects of miR-146b-3p. Conclusions: Overexpression of miR-146b-5p and miR-146b-3p is associated with PTC metastasis. MiR-146b-3p enhances cell invasion and metastasis more obviously than miR-146b-5p through the suppression of the NF2 gene. These findings suggest a potential diagnostic and therapeutic value of these miRNAs in PTC metastasis.

Dataset Information

MicroRNA-203a-3p may prevent the development of thyroid papillary carcinoma via repressing MAP3K1 and activating autophagy.

Background

Methods

Results

Conclusion

Publications

MicroRNA-203a-3p may prevent the development of thyroid papillary carcinoma via repressing MAP3K1 and activating autophagy.

Similar Datasets

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