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LncRNA LOXL1‐AS1 facilitates the tumorigenesis and stemness of gastric carcinoma via regulation of miR‐708‐5p/USF1 pathway
OBJECTIVES: As one of the most life‐threatening malignancies, gastric cancer is the third contributor of cancer mortalities globally. Increasing studies have proven the regulatory roles of lncRNAs in the development of diverse malignant tumours. But little is known about its function and molecular m...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6869681/ https://www.ncbi.nlm.nih.gov/pubmed/31468594 http://dx.doi.org/10.1111/cpr.12687 |
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author | Sun, Qi Li, Jian Li, Fan Li, Huanqin Bei, Songhua Zhang, Xiaohong Feng, Li |
author_facet | Sun, Qi Li, Jian Li, Fan Li, Huanqin Bei, Songhua Zhang, Xiaohong Feng, Li |
author_sort | Sun, Qi |
collection | PubMed |
description | OBJECTIVES: As one of the most life‐threatening malignancies, gastric cancer is the third contributor of cancer mortalities globally. Increasing studies have proven the regulatory roles of lncRNAs in the development of diverse malignant tumours. But little is known about its function and molecular mechanism in gastric carcinoma. MATERIALS AND METHODS: RT‐qPCR was performed to measure the expression pattern of LOXL1‐AS1 in gastric cancer. To ascertain its definite role, CCK‐8, EdU, Western blot, transwell and sphere formation assays were adopted. RNA pull‐down, RIP, ChIP and luciferase reporter assays were carried out to investigate the molecular mechanism of LOXL1‐AS1 in gastric carcinoma. RESULTS: LOXL1‐AS1 was highly expressed in tissues and cells of gastric cancer. The upregulation of LOXL1‐AS1 predicted poor prognosis in gastric carcinoma. Our findings demonstrated that LOXL1‐AS1 accelerated the deterioration of gastric cancer by inducing cell proliferation, migration, EMT and stemness. Moreover, the expression of USF1 in gastric cancer was higher than in normal control and LOXL1‐AS1 negatively modulated USF1. Functionally, LOXL1‐AS1 acted as a ceRNA to upregulate USF1 via sponging miR‐708‐5p. Besides, we confirmed USF1 promoted the transcription of stemness marker SOX2. Rescue experiments testified the stimulative role of LOXL1‐AS1/miR‐708‐5p/USF1 pathway in gastric cancer progression. It was also validated that LOXL1‐AS1 facilitated cell growth of gastric carcinoma in vivo. CONCLUSIONS: Our study unravelled that LOXL1‐AS1/miR‐708‐5p/USF1 pathway contributed to the development of gastric cancer. |
format | Online Article Text |
id | pubmed-6869681 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68696812020-03-13 LncRNA LOXL1‐AS1 facilitates the tumorigenesis and stemness of gastric carcinoma via regulation of miR‐708‐5p/USF1 pathway Sun, Qi Li, Jian Li, Fan Li, Huanqin Bei, Songhua Zhang, Xiaohong Feng, Li Cell Prolif Original Articles OBJECTIVES: As one of the most life‐threatening malignancies, gastric cancer is the third contributor of cancer mortalities globally. Increasing studies have proven the regulatory roles of lncRNAs in the development of diverse malignant tumours. But little is known about its function and molecular mechanism in gastric carcinoma. MATERIALS AND METHODS: RT‐qPCR was performed to measure the expression pattern of LOXL1‐AS1 in gastric cancer. To ascertain its definite role, CCK‐8, EdU, Western blot, transwell and sphere formation assays were adopted. RNA pull‐down, RIP, ChIP and luciferase reporter assays were carried out to investigate the molecular mechanism of LOXL1‐AS1 in gastric carcinoma. RESULTS: LOXL1‐AS1 was highly expressed in tissues and cells of gastric cancer. The upregulation of LOXL1‐AS1 predicted poor prognosis in gastric carcinoma. Our findings demonstrated that LOXL1‐AS1 accelerated the deterioration of gastric cancer by inducing cell proliferation, migration, EMT and stemness. Moreover, the expression of USF1 in gastric cancer was higher than in normal control and LOXL1‐AS1 negatively modulated USF1. Functionally, LOXL1‐AS1 acted as a ceRNA to upregulate USF1 via sponging miR‐708‐5p. Besides, we confirmed USF1 promoted the transcription of stemness marker SOX2. Rescue experiments testified the stimulative role of LOXL1‐AS1/miR‐708‐5p/USF1 pathway in gastric cancer progression. It was also validated that LOXL1‐AS1 facilitated cell growth of gastric carcinoma in vivo. CONCLUSIONS: Our study unravelled that LOXL1‐AS1/miR‐708‐5p/USF1 pathway contributed to the development of gastric cancer. John Wiley and Sons Inc. 2019-08-29 /pmc/articles/PMC6869681/ /pubmed/31468594 http://dx.doi.org/10.1111/cpr.12687 Text en © 2019 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Sun, Qi Li, Jian Li, Fan Li, Huanqin Bei, Songhua Zhang, Xiaohong Feng, Li LncRNA LOXL1‐AS1 facilitates the tumorigenesis and stemness of gastric carcinoma via regulation of miR‐708‐5p/USF1 pathway |
title | LncRNA LOXL1‐AS1 facilitates the tumorigenesis and stemness of gastric carcinoma via regulation of miR‐708‐5p/USF1 pathway |
title_full | LncRNA LOXL1‐AS1 facilitates the tumorigenesis and stemness of gastric carcinoma via regulation of miR‐708‐5p/USF1 pathway |
title_fullStr | LncRNA LOXL1‐AS1 facilitates the tumorigenesis and stemness of gastric carcinoma via regulation of miR‐708‐5p/USF1 pathway |
title_full_unstemmed | LncRNA LOXL1‐AS1 facilitates the tumorigenesis and stemness of gastric carcinoma via regulation of miR‐708‐5p/USF1 pathway |
title_short | LncRNA LOXL1‐AS1 facilitates the tumorigenesis and stemness of gastric carcinoma via regulation of miR‐708‐5p/USF1 pathway |
title_sort | lncrna loxl1‐as1 facilitates the tumorigenesis and stemness of gastric carcinoma via regulation of mir‐708‐5p/usf1 pathway |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6869681/ https://www.ncbi.nlm.nih.gov/pubmed/31468594 http://dx.doi.org/10.1111/cpr.12687 |
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