C-Myc-activated long non-coding RNA LINC01050 promotes gastric cancer growth and metastasis by sponging miR-7161-3p to regulate SPZ1 expression

Abstract Background Growing evidence shows that long non-coding RNAs (lncRNAs) play significant roles in cancer development. However, the functions of most lncRNAs in human gastric cancer are still not fully understood. Here, we explored the role of a novel c-Myc-activated lncRNA, LINC01050, in gast...

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Autores principales:	Ziwei Ji, Tianbin Tang, Mengxia Chen, Buyuan Dong, Wenjing Sun, Nan Wu, Hao Chen, Qian Feng, Xingyi Yang, Rong Jin, Lei Jiang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Gastric cancer C-Myc LINC01050 miR-7161-3p SPZ1 Metastasis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/f3c663ed09ed4f689acb97cad1cf0f94
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spelling	oai:doaj.org-article:f3c663ed09ed4f689acb97cad1cf0f942021-11-14T12:15:26ZC-Myc-activated long non-coding RNA LINC01050 promotes gastric cancer growth and metastasis by sponging miR-7161-3p to regulate SPZ1 expression10.1186/s13046-021-02155-71756-9966https://doaj.org/article/f3c663ed09ed4f689acb97cad1cf0f942021-11-01T00:00:00Zhttps://doi.org/10.1186/s13046-021-02155-7https://doaj.org/toc/1756-9966Abstract Background Growing evidence shows that long non-coding RNAs (lncRNAs) play significant roles in cancer development. However, the functions of most lncRNAs in human gastric cancer are still not fully understood. Here, we explored the role of a novel c-Myc-activated lncRNA, LINC01050, in gastric cancer progression. Methods The expression of LINC01050 in the context of gastric cancer was assessed using The Cancer Genome Atlas datasets. Its functions in gastric cancer were investigated through gain- and loss-of-function experiments combined with the Cell Counting Kit-8 assays, colony-forming assays, Transwell assays, flow cytometry, Western blot analyses, and xenograft tumor and mouse metastasis models. Potential LINC01050 transcription activators were screened via bioinformatics and validated by chromatin immunoprecipitation and luciferase assays. The interaction between LINC01050 and miR-7161-3p and the targets of miR-7161-3p were predicted by bioinformatics analysis and confirmed by a luciferase assay, RNA immunoprecipitation, RNA pull-down, and rescue experiments. Results LINC01050 was significantly up-regulated in gastric cancer, and its high expression was positively correlated with a poor prognosis. The transcription factor c-Myc was found to directly bind to the LINC01050 promoter region and activate its transcription. Furthermore, overexpression of LINC01050 was confirmed to promote gastric cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro and tumor growth in vivo. At the same time, its knockdown inhibited gastric cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro along with tumor growth and metastasis in vivo. Moreover, mechanistic investigations revealed that LINC01050 functions as a molecular sponge to absorb cytosolic miR-7161-3p, which reduces the miR-7161-3p-mediated translational repression of SPZ1, thus contributing to gastric cancer progression. Conclusions Taken together, our results identified a novel gastric cancer-associated lncRNA, LINC01050, which is activated by c-Myc. LINC01050 may be considered a potential therapeutic target for gastric cancer.Ziwei JiTianbin TangMengxia ChenBuyuan DongWenjing SunNan WuHao ChenQian FengXingyi YangRong JinLei JiangBMCarticleGastric cancerC-MycLINC01050miR-7161-3pSPZ1MetastasisNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJournal of Experimental & Clinical Cancer Research, Vol 40, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Gastric cancer C-Myc LINC01050 miR-7161-3p SPZ1 Metastasis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Gastric cancer C-Myc LINC01050 miR-7161-3p SPZ1 Metastasis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Ziwei Ji Tianbin Tang Mengxia Chen Buyuan Dong Wenjing Sun Nan Wu Hao Chen Qian Feng Xingyi Yang Rong Jin Lei Jiang C-Myc-activated long non-coding RNA LINC01050 promotes gastric cancer growth and metastasis by sponging miR-7161-3p to regulate SPZ1 expression
description	Abstract Background Growing evidence shows that long non-coding RNAs (lncRNAs) play significant roles in cancer development. However, the functions of most lncRNAs in human gastric cancer are still not fully understood. Here, we explored the role of a novel c-Myc-activated lncRNA, LINC01050, in gastric cancer progression. Methods The expression of LINC01050 in the context of gastric cancer was assessed using The Cancer Genome Atlas datasets. Its functions in gastric cancer were investigated through gain- and loss-of-function experiments combined with the Cell Counting Kit-8 assays, colony-forming assays, Transwell assays, flow cytometry, Western blot analyses, and xenograft tumor and mouse metastasis models. Potential LINC01050 transcription activators were screened via bioinformatics and validated by chromatin immunoprecipitation and luciferase assays. The interaction between LINC01050 and miR-7161-3p and the targets of miR-7161-3p were predicted by bioinformatics analysis and confirmed by a luciferase assay, RNA immunoprecipitation, RNA pull-down, and rescue experiments. Results LINC01050 was significantly up-regulated in gastric cancer, and its high expression was positively correlated with a poor prognosis. The transcription factor c-Myc was found to directly bind to the LINC01050 promoter region and activate its transcription. Furthermore, overexpression of LINC01050 was confirmed to promote gastric cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro and tumor growth in vivo. At the same time, its knockdown inhibited gastric cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro along with tumor growth and metastasis in vivo. Moreover, mechanistic investigations revealed that LINC01050 functions as a molecular sponge to absorb cytosolic miR-7161-3p, which reduces the miR-7161-3p-mediated translational repression of SPZ1, thus contributing to gastric cancer progression. Conclusions Taken together, our results identified a novel gastric cancer-associated lncRNA, LINC01050, which is activated by c-Myc. LINC01050 may be considered a potential therapeutic target for gastric cancer.
format	article
author	Ziwei Ji Tianbin Tang Mengxia Chen Buyuan Dong Wenjing Sun Nan Wu Hao Chen Qian Feng Xingyi Yang Rong Jin Lei Jiang
author_facet	Ziwei Ji Tianbin Tang Mengxia Chen Buyuan Dong Wenjing Sun Nan Wu Hao Chen Qian Feng Xingyi Yang Rong Jin Lei Jiang
author_sort	Ziwei Ji
title	C-Myc-activated long non-coding RNA LINC01050 promotes gastric cancer growth and metastasis by sponging miR-7161-3p to regulate SPZ1 expression
title_short	C-Myc-activated long non-coding RNA LINC01050 promotes gastric cancer growth and metastasis by sponging miR-7161-3p to regulate SPZ1 expression
title_full	C-Myc-activated long non-coding RNA LINC01050 promotes gastric cancer growth and metastasis by sponging miR-7161-3p to regulate SPZ1 expression
title_fullStr	C-Myc-activated long non-coding RNA LINC01050 promotes gastric cancer growth and metastasis by sponging miR-7161-3p to regulate SPZ1 expression
title_full_unstemmed	C-Myc-activated long non-coding RNA LINC01050 promotes gastric cancer growth and metastasis by sponging miR-7161-3p to regulate SPZ1 expression
title_sort	c-myc-activated long non-coding rna linc01050 promotes gastric cancer growth and metastasis by sponging mir-7161-3p to regulate spz1 expression
publisher	BMC
publishDate	2021
url	https://doaj.org/article/f3c663ed09ed4f689acb97cad1cf0f94
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C-Myc-activated long non-coding RNA LINC01050 promotes gastric cancer growth and metastasis by sponging miR-7161-3p to regulate SPZ1 expression

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