Cargando…

MALAT1 promotes gastric adenocarcinoma through the MALAT1/miR-181a-5p/AKT3 axis

Gastric adenocarcinoma, which originates from the gastric mucosal epithelium, has the highest incidence among various malignant tumours in China. As a crucial long non-coding RNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been suggested to play an important role in many tum...

Descripción completa

Detalles Bibliográficos
Autores principales: Lu, Zhengmao, Luo, Tianhang, Pang, Tao, Du, Zongxin, Yin, Xiaoyi, Cui, Hangtian, Fang, Guoen, Xue, Xuchao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769293/
https://www.ncbi.nlm.nih.gov/pubmed/31480991
http://dx.doi.org/10.1098/rsob.190095
_version_ 1783455214645280768
author Lu, Zhengmao
Luo, Tianhang
Pang, Tao
Du, Zongxin
Yin, Xiaoyi
Cui, Hangtian
Fang, Guoen
Xue, Xuchao
author_facet Lu, Zhengmao
Luo, Tianhang
Pang, Tao
Du, Zongxin
Yin, Xiaoyi
Cui, Hangtian
Fang, Guoen
Xue, Xuchao
author_sort Lu, Zhengmao
collection PubMed
description Gastric adenocarcinoma, which originates from the gastric mucosal epithelium, has the highest incidence among various malignant tumours in China. As a crucial long non-coding RNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been suggested to play an important role in many tumours. Here, we aimed to investigate the role and underlying mechanism of MALAT1 in gastric adenocarcinoma. Quantitative reverse transcription polymerase chain reaction was applied to determine the expression levels of MALAT1 in serum and cell lines. A CCK-8 assay and a clonogenic survival assay were used to examine cell proliferation and apoptosis. The protein level of RAC-γ serine/threonine-specific protein kinase (AKT3) was determined by western blot. Our results showed that MALAT1 was highly expressed in the serum of patients with gastric adenocarcinoma and in cell lines. Downregulating MALAT1 inhibited proliferation and promoted apoptosis of MGC-803 cells. In addition, MALAT1 directly targeted and decreased the expression of miR-181a-5p, which in turn upregulated the expression of AKT3. Further, overexpressing miR-181a-5p or directly inhibiting the AKT pathway with the inhibitor ipatasertib exhibited similar effects to MALAT1 knockdown. Our research proposes a novel mechanism where the role of MALAT1 is dependent on the MALAT1/miR-181a-5p/AKT3 axis. MALAT1 competes with AKT3 for miR-181a-5p binding, thereby upregulating the AKT3 protein level and ultimately promoting the growth of gastric adenocarcinoma.
format Online
Article
Text
id pubmed-6769293
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher The Royal Society
record_format MEDLINE/PubMed
spelling pubmed-67692932019-10-03 MALAT1 promotes gastric adenocarcinoma through the MALAT1/miR-181a-5p/AKT3 axis Lu, Zhengmao Luo, Tianhang Pang, Tao Du, Zongxin Yin, Xiaoyi Cui, Hangtian Fang, Guoen Xue, Xuchao Open Biol Research Gastric adenocarcinoma, which originates from the gastric mucosal epithelium, has the highest incidence among various malignant tumours in China. As a crucial long non-coding RNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been suggested to play an important role in many tumours. Here, we aimed to investigate the role and underlying mechanism of MALAT1 in gastric adenocarcinoma. Quantitative reverse transcription polymerase chain reaction was applied to determine the expression levels of MALAT1 in serum and cell lines. A CCK-8 assay and a clonogenic survival assay were used to examine cell proliferation and apoptosis. The protein level of RAC-γ serine/threonine-specific protein kinase (AKT3) was determined by western blot. Our results showed that MALAT1 was highly expressed in the serum of patients with gastric adenocarcinoma and in cell lines. Downregulating MALAT1 inhibited proliferation and promoted apoptosis of MGC-803 cells. In addition, MALAT1 directly targeted and decreased the expression of miR-181a-5p, which in turn upregulated the expression of AKT3. Further, overexpressing miR-181a-5p or directly inhibiting the AKT pathway with the inhibitor ipatasertib exhibited similar effects to MALAT1 knockdown. Our research proposes a novel mechanism where the role of MALAT1 is dependent on the MALAT1/miR-181a-5p/AKT3 axis. MALAT1 competes with AKT3 for miR-181a-5p binding, thereby upregulating the AKT3 protein level and ultimately promoting the growth of gastric adenocarcinoma. The Royal Society 2019-09-04 /pmc/articles/PMC6769293/ /pubmed/31480991 http://dx.doi.org/10.1098/rsob.190095 Text en © 2019 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Research
Lu, Zhengmao
Luo, Tianhang
Pang, Tao
Du, Zongxin
Yin, Xiaoyi
Cui, Hangtian
Fang, Guoen
Xue, Xuchao
MALAT1 promotes gastric adenocarcinoma through the MALAT1/miR-181a-5p/AKT3 axis
title MALAT1 promotes gastric adenocarcinoma through the MALAT1/miR-181a-5p/AKT3 axis
title_full MALAT1 promotes gastric adenocarcinoma through the MALAT1/miR-181a-5p/AKT3 axis
title_fullStr MALAT1 promotes gastric adenocarcinoma through the MALAT1/miR-181a-5p/AKT3 axis
title_full_unstemmed MALAT1 promotes gastric adenocarcinoma through the MALAT1/miR-181a-5p/AKT3 axis
title_short MALAT1 promotes gastric adenocarcinoma through the MALAT1/miR-181a-5p/AKT3 axis
title_sort malat1 promotes gastric adenocarcinoma through the malat1/mir-181a-5p/akt3 axis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769293/
https://www.ncbi.nlm.nih.gov/pubmed/31480991
http://dx.doi.org/10.1098/rsob.190095
work_keys_str_mv AT luzhengmao malat1promotesgastricadenocarcinomathroughthemalat1mir181a5pakt3axis
AT luotianhang malat1promotesgastricadenocarcinomathroughthemalat1mir181a5pakt3axis
AT pangtao malat1promotesgastricadenocarcinomathroughthemalat1mir181a5pakt3axis
AT duzongxin malat1promotesgastricadenocarcinomathroughthemalat1mir181a5pakt3axis
AT yinxiaoyi malat1promotesgastricadenocarcinomathroughthemalat1mir181a5pakt3axis
AT cuihangtian malat1promotesgastricadenocarcinomathroughthemalat1mir181a5pakt3axis
AT fangguoen malat1promotesgastricadenocarcinomathroughthemalat1mir181a5pakt3axis
AT xuexuchao malat1promotesgastricadenocarcinomathroughthemalat1mir181a5pakt3axis