Dataset Information

Long Non-Coding RNA LUCAT1 Promotes Progression of Thyroid Carcinoma by Reinforcing ADAM10 Expression Through Sequestering microRNA-493.

ABSTRACT: Background:Long non-coding RNA (lncRNA) LUCAT1 has recently been recognized as an oncogene in several malignancies. This study was launched to probe its role in thyroid carcinoma (TC) development and the implicated molecules. Methods:LUCAT1 expression in TC cell lines and in normal thyroid follicular epithelial cell line Nthy-ori3-1 was determined by RT-qPCR. Binding relationships between LUCAT1 and microRNA (miR)-493, and between miR-493 and a disintegrin and metalloproteinase-10 (ADAM10) were predicted on a bioinformatics system and then validated through luciferase reporter gene assays. Expression of miR-493 and ADAM10 in TC cells was determined. Gain- and loss-of functions of LUCAT1, miR-493 and ADAM10 were performed to explore their influences on the behaviors of TC cells. Xenograft tumors were induced in nude mice for in vivo studies. Results:LUCAT1 and ADAM10 were highly expressed, while miR-493 was poorly expressed in TC cell lines. LUCAT1 served as a miR-493 sponge to upregulate ADAM10 expression. Silencing of LUCAT1 discouraged proliferation, invasion, and migration but triggered apoptosis of TC cells. By contrast, these changes were abrogated by further miR-493 inhibition or ADAM10 upregulation. The in vitro experiment results were reproduced in vivo. In addition, miR-493 inhibition or ADAM10 overexpression was found to increase the phosphorylation of STAT3 in cells. Conclusion:This study evidenced that LUCAT1 increases ADAM10 expression through sequestering miR-493, leading to JAK-STAT activation and TC cell growth and metastasis. LUCAT1 and ADAM10 may serve as therapeutic targets for TC treatment.

SUBMITTER: Xiong G

PROVIDER: S-EPMC7569253 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Long Non-Coding RNA LUCAT1 Promotes Progression of Thyroid Carcinoma by Reinforcing ADAM10 Expression Through Sequestering microRNA-493.

Xiong Guofeng G Chen Jiaming J Wu Zhen Z He Shizhi S Lian Meng M Fang Jugao J

International journal of general medicine 20201014

<h4>Background</h4>Long non-coding RNA (lncRNA) LUCAT1 has recently been recognized as an oncogene in several malignancies. This study was launched to probe its role in thyroid carcinoma (TC) development and the implicated molecules.<h4>Methods</h4>LUCAT1 expression in TC cell lines and in normal thyroid follicular epithelial cell line Nthy-ori3-1 was determined by RT-qPCR. Binding relationships between LUCAT1 and microRNA (miR)-493, and between miR-493 and a disintegrin and metalloproteinase-10 ...[more]

PMID: 33116777

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Project description:Long non-coding RNAs (lncRNAs) are important biological factors that contribute to the initiation and progression of different types of cancer, including gastric, bladder and colorectal cancer. Small nucleolar RNA host gene 3 (SNHG3) has been implicated in prostate cancer (PCa) progression. However, the expression pattern and function of SNHG3 in PCa remain unclear, impeding the development of novel treatment strategies for this cancer. The present study aimed to investigate a combination of molecular and biochemical approaches to determine the role of SNHG3 in patients at different stages of disease, and elucidate the pathway by which SNHG3 affects PCa progression. A Cell Counting Kit-8 assay was used to assess cell proliferation. Transwell assays were used to analyze cell migration and invasion. Reverse transcription-quantitative PCR and western blotting were used to evaluate the expression levels of RNAs and proteins, respectively. The results demonstrated that SNHG3 expression was upregulated in PCa tissues downloaded from The Cancer Genome Atlas database, which was associated with poor prognosis. Furthermore, cell proliferation, migration and invasion were significantly inhibited following SNHG3 knockdown in vitro, the effects of which were reversed following overexpression of SNHG3 in PCa cells. Bioinformatic analysis revealed that microRNA (miRNA/miR)-1827 was a downstream target of SNHG3. The direct interaction between SNHG3 and miR-1827 was validated via the dual-luciferase reporter and RNA immunoprecipitation assays. Pearson's correlation analysis demonstrated that SNHG3 expression was negatively correlated with miR-1827 expression at different stages of PCa. Furthermore, rescue assays indicated that cotransfection with small interfering-SNHG3 and miR-1827 inhibitor reversed the effects of SNHG3 knockdown on cell proliferation, migration and invasion. In addition, SNHG3 knockdown in vivo suppressed tumor growth. Notably, lncRNA SNHG3 promoted PCa progression through miR-1827 via the Wnt/AKT/mTOR pathway. Taken together, the results of the present study suggest that SNHG3 promotes PCa progression by sponging miR-1827, indicating that SNHG3 may be a promising diagnostic and therapeutic target of PCa.

Dataset Information

Long Non-Coding RNA LUCAT1 Promotes Progression of Thyroid Carcinoma by Reinforcing ADAM10 Expression Through Sequestering microRNA-493.

Publications

Long Non-Coding RNA LUCAT1 Promotes Progression of Thyroid Carcinoma by Reinforcing ADAM10 Expression Through Sequestering microRNA-493.

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