Dataset Information

LncRNA HOXA11-AS accumulation-induced microRNA-761 downregulation regulates cell growth by targeting TRIM29 in papillary thyroid cancer.

ABSTRACT: Increasing evidence demonstrate that dysregulated microRNAs (miRNAs) are involved in carcinogenesis and tumor progression in papillary thyroid cancer (PTC). However, the specific miR-761 in cancer remains largely unknown. In this study, we reported for the first that miR-761 expression was down-regulated in PTC tissues and cell lines, and its decrease was associated with tumor size and TNM stage. Gain- and loss-of function experiments revealed that miR-761 inhibited cell proliferation, colony formation and cell cycle progression in vitro and in vivo. Moreover, TRIM29 was identified as a direct downstream target of miR-761 in PTC cells and mediated the functional effects of miR-761 in PTC. Restoration of TRIM29 expression at least partially abolished the biological effects of miR-761 on PTC cells. Furthermore, overexpression of lncRNA HOXA11-AS was inversely correlated with miR-761 expression in PTC tissues. LncRNA HOXA11-AS could modulate the miR-761 expression and regulate cellular behaviors. Taken together, this research supports the first evidence that lncRNA HOXA11-AS-reguated miR-761 plays a functional role in inhibiting PTC progression by targeting TRIM29 and represent a promising therapeutic strategy for patients with PTC.

SUBMITTER: Yin X

PROVIDER: S-EPMC6895523 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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LncRNA HOXA11-AS accumulation-induced microRNA-761 downregulation regulates cell growth by targeting TRIM29 in papillary thyroid cancer.

Yin Xiangdang X Zhang Jian J Li Chaojun C Zhang Zhe Z Jin Tong T Song Liyou L Zhang Rui R Wang Wei W Tao Youmao Y Wang Xiaochun X

American journal of translational research 20191115 11

Increasing evidence demonstrate that dysregulated microRNAs (miRNAs) are involved in carcinogenesis and tumor progression in papillary thyroid cancer (PTC). However, the specific miR-761 in cancer remains largely unknown. In this study, we reported for the first that miR-761 expression was down-regulated in PTC tissues and cell lines, and its decrease was associated with tumor size and TNM stage. Gain- and loss-of function experiments revealed that miR-761 inhibited cell proliferation, colony fo ...[more]

PMID: 31814890

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Project description:OBJECTIVES:Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer, which accounts for 80-90% of all thyroid cancer cases. Though the pathological mechanism hasn't been fully understood, it is reported that both environmental and genetic factor may contribute to the PTC susceptibility. MicroRNAs (miRNAs) are small non-coding RNA molecules which function as the suppressors to participate in a variety of biological processes. Accumulating evidence suggests that polymorphisms of miRNAs were associated with the tumorigenesis of various cancers, including PTC. In this article, we focus on the association between four common microRNA polymorphisms (miR-146a, miR-608, miR-933, and miR-149) and PTC risk in a Han Chinese population. METHODS:In this case-control study, we recruited 1,398 participants in total, including 369 PTC patients, 278 patients with thyroid benign nodules (BN) and 751 normal controls. The miRNAs polymorphisms were genotyped and analyzed by using MALDI-TOF mass spectrometry. The odd ratios and their 95% confidence interval (95% CI) were calculated to evaluate the association between miRNAs polymorphisms and PTC risk. Furthermore, a meta-analysis based on previous studies was conducted to comprehensively assess the diagnostic performance of miR-146a in the PTC diagnosis. RESULTS:The miR-146a polymorphisms were shown to be significantly correlated with elevated risk of PTC under the heterozygous, homozygous, dominant and allelic models by comparing the genotype distribution between PTC cases and healthy controls, as well as between PTC cases and BN cases. However, the result of meta-analysis showed no significant association between miR-146a polymorphisms and PTC risk. CONCLUSIONS:Our study indicated that the miR-146a polymorphism was significantly associated with PTC risk. In contrast, meta-analysis revealed no evidence of association between miR-146a variants and PTC risk. Further studies are required to elucidate the role of miR-146a in the etiology of PTC.

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

LncRNA HOXA11-AS accumulation-induced microRNA-761 downregulation regulates cell growth by targeting TRIM29 in papillary thyroid cancer.

Publications

LncRNA HOXA11-AS accumulation-induced microRNA-761 downregulation regulates cell growth by targeting TRIM29 in papillary thyroid cancer.

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