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Up-regulation of CRKL by microRNA-335 methylation is associated with poor prognosis in gastric cancer
BACKGROUND: MicroRNAs have been suggested to play a vital role in regulating carcinogenesis, tumor progression and invasion. MiR-335 is involved in suppressing metastasis and invasion in various human cancers. However, the mechanisms responsible for the aberrant expression of miR-335 in gastric canc...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5314703/ https://www.ncbi.nlm.nih.gov/pubmed/28239297 http://dx.doi.org/10.1186/s12935-017-0387-9 |
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author | Zhang, Jia-kui Li, Yong-shuang Zhang, Chun-dong Dai, Dong-qiu |
author_facet | Zhang, Jia-kui Li, Yong-shuang Zhang, Chun-dong Dai, Dong-qiu |
author_sort | Zhang, Jia-kui |
collection | PubMed |
description | BACKGROUND: MicroRNAs have been suggested to play a vital role in regulating carcinogenesis, tumor progression and invasion. MiR-335 is involved in suppressing metastasis and invasion in various human cancers. However, the mechanisms responsible for the aberrant expression of miR-335 in gastric cancer (GC) remain unknown. METHODS: Expression of miR-335 in four GC cell lines and 231 GC tissues was determined by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). DNA methylation status in the CpG islands upstream of miR-335 in GC cell lines and tissues was determined by methylation-specific PCR and bisulfite sequence-PCR. The effects of the demethylating agent 5-aza-2′-deoxycytidine on cell proliferation, apoptosis, cell cycle, migration, and invasion were investigated in GC cell lines. RESULTS: Cancer-specific methylation was detected in the upstream CpG-rich regions of miR-335, which dramatically silenced its transcriptional activity in GC cell lines and tissues. Low levels of miR-335 expression and high levels of miR-335 methylation in GC tissues were associated with poor clinical features and prognosis. Restoration of miR-335 expression in GC cells promoted cell apoptosis, inhibited tumor cell migration, invasion, and proliferation, and arrested the cell cycle at G0/G1 phase. Overexpression of miR-335 significantly reduced the activity of a luciferase reporter containing the 3′ untranslated region of V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL). CONCLUSIONS: MiR-335 functions as a tumor suppressor and may be silenced by promoter hypermethylation. It plays a role in inhibiting tumor cell migration, invasion, and proliferation, arresting the cell cycle at G0/G1 phase, and promoting apoptosis in GC cells through targeting CRKL. |
format | Online Article Text |
id | pubmed-5314703 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-53147032017-02-24 Up-regulation of CRKL by microRNA-335 methylation is associated with poor prognosis in gastric cancer Zhang, Jia-kui Li, Yong-shuang Zhang, Chun-dong Dai, Dong-qiu Cancer Cell Int Primary Research BACKGROUND: MicroRNAs have been suggested to play a vital role in regulating carcinogenesis, tumor progression and invasion. MiR-335 is involved in suppressing metastasis and invasion in various human cancers. However, the mechanisms responsible for the aberrant expression of miR-335 in gastric cancer (GC) remain unknown. METHODS: Expression of miR-335 in four GC cell lines and 231 GC tissues was determined by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). DNA methylation status in the CpG islands upstream of miR-335 in GC cell lines and tissues was determined by methylation-specific PCR and bisulfite sequence-PCR. The effects of the demethylating agent 5-aza-2′-deoxycytidine on cell proliferation, apoptosis, cell cycle, migration, and invasion were investigated in GC cell lines. RESULTS: Cancer-specific methylation was detected in the upstream CpG-rich regions of miR-335, which dramatically silenced its transcriptional activity in GC cell lines and tissues. Low levels of miR-335 expression and high levels of miR-335 methylation in GC tissues were associated with poor clinical features and prognosis. Restoration of miR-335 expression in GC cells promoted cell apoptosis, inhibited tumor cell migration, invasion, and proliferation, and arrested the cell cycle at G0/G1 phase. Overexpression of miR-335 significantly reduced the activity of a luciferase reporter containing the 3′ untranslated region of V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL). CONCLUSIONS: MiR-335 functions as a tumor suppressor and may be silenced by promoter hypermethylation. It plays a role in inhibiting tumor cell migration, invasion, and proliferation, arresting the cell cycle at G0/G1 phase, and promoting apoptosis in GC cells through targeting CRKL. BioMed Central 2017-02-16 /pmc/articles/PMC5314703/ /pubmed/28239297 http://dx.doi.org/10.1186/s12935-017-0387-9 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Primary Research Zhang, Jia-kui Li, Yong-shuang Zhang, Chun-dong Dai, Dong-qiu Up-regulation of CRKL by microRNA-335 methylation is associated with poor prognosis in gastric cancer |
title | Up-regulation of CRKL by microRNA-335 methylation is associated with poor prognosis in gastric cancer |
title_full | Up-regulation of CRKL by microRNA-335 methylation is associated with poor prognosis in gastric cancer |
title_fullStr | Up-regulation of CRKL by microRNA-335 methylation is associated with poor prognosis in gastric cancer |
title_full_unstemmed | Up-regulation of CRKL by microRNA-335 methylation is associated with poor prognosis in gastric cancer |
title_short | Up-regulation of CRKL by microRNA-335 methylation is associated with poor prognosis in gastric cancer |
title_sort | up-regulation of crkl by microrna-335 methylation is associated with poor prognosis in gastric cancer |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5314703/ https://www.ncbi.nlm.nih.gov/pubmed/28239297 http://dx.doi.org/10.1186/s12935-017-0387-9 |
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