Cargando…

miR-492 promotes chemoresistance to CDDP and metastasis by targeting inhibiting DNMT3B and induces stemness in gastric cancer

Objective: Metastasis and chemoresistance indicate treatment fail and progresses in gastric cancer (GC) patients. However, the molecular mechanisms of chemoresistance and metastasis remain unclear in GC. Thus, identifying the biological indicators of chemoresistance and metastasis is particularly im...

Descripción completa

Detalles Bibliográficos
Autores principales: Wu, Shuai, Xie, Jian, Shi, Hao, Wang, Zi-wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064790/
https://www.ncbi.nlm.nih.gov/pubmed/32065219
http://dx.doi.org/10.1042/BSR20194342
_version_ 1783504933661704192
author Wu, Shuai
Xie, Jian
Shi, Hao
Wang, Zi-wei
author_facet Wu, Shuai
Xie, Jian
Shi, Hao
Wang, Zi-wei
author_sort Wu, Shuai
collection PubMed
description Objective: Metastasis and chemoresistance indicate treatment fail and progresses in gastric cancer (GC) patients. However, the molecular mechanisms of chemoresistance and metastasis remain unclear in GC. Thus, identifying the biological indicators of chemoresistance and metastasis is particularly important. Materials and methods: We establish a role for miR-492 in GC metastasis and chemoresistance through experiments in vitro and in vivo. Results: We identified miR-492 overexpression in GC specimens and cell lines, the miR-492 expression level was inversely correlated with the prognosis of GC patients. The inhibition of miR-492 suppressed GC cell invasion and enhanced the sensitivity of gastric cancer cells to CDDP treatment. In contrast, miR-492 overexpression significantly stimulated GC cell invasion and contributed to chemoresistance development. In addition, our research results indicated that the inhibition of miR-492 stimulates GC stemness, and the overexpression of miR-492 induces GC stemness. Importantly, our experiments demonstrated that miR-492 inhibitor suppressed tumor formation, and the combination treatment of miR-492 inhibitor and CDDP significantly inhibited tumor growth in vivo. Furthermore, we demonstrated that miR-492 exerts its anticancer role by targeting DNMT3B in GC. Conclusions: Our results suggested that inhibiting miR-492 is a novel strategy to control tumor metastasis and chemoresistance in GC.
format Online
Article
Text
id pubmed-7064790
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Portland Press Ltd.
record_format MEDLINE/PubMed
spelling pubmed-70647902020-03-18 miR-492 promotes chemoresistance to CDDP and metastasis by targeting inhibiting DNMT3B and induces stemness in gastric cancer Wu, Shuai Xie, Jian Shi, Hao Wang, Zi-wei Biosci Rep Cancer Objective: Metastasis and chemoresistance indicate treatment fail and progresses in gastric cancer (GC) patients. However, the molecular mechanisms of chemoresistance and metastasis remain unclear in GC. Thus, identifying the biological indicators of chemoresistance and metastasis is particularly important. Materials and methods: We establish a role for miR-492 in GC metastasis and chemoresistance through experiments in vitro and in vivo. Results: We identified miR-492 overexpression in GC specimens and cell lines, the miR-492 expression level was inversely correlated with the prognosis of GC patients. The inhibition of miR-492 suppressed GC cell invasion and enhanced the sensitivity of gastric cancer cells to CDDP treatment. In contrast, miR-492 overexpression significantly stimulated GC cell invasion and contributed to chemoresistance development. In addition, our research results indicated that the inhibition of miR-492 stimulates GC stemness, and the overexpression of miR-492 induces GC stemness. Importantly, our experiments demonstrated that miR-492 inhibitor suppressed tumor formation, and the combination treatment of miR-492 inhibitor and CDDP significantly inhibited tumor growth in vivo. Furthermore, we demonstrated that miR-492 exerts its anticancer role by targeting DNMT3B in GC. Conclusions: Our results suggested that inhibiting miR-492 is a novel strategy to control tumor metastasis and chemoresistance in GC. Portland Press Ltd. 2020-03-09 /pmc/articles/PMC7064790/ /pubmed/32065219 http://dx.doi.org/10.1042/BSR20194342 Text en © 2020 The Author(s). https://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).
spellingShingle Cancer
Wu, Shuai
Xie, Jian
Shi, Hao
Wang, Zi-wei
miR-492 promotes chemoresistance to CDDP and metastasis by targeting inhibiting DNMT3B and induces stemness in gastric cancer
title miR-492 promotes chemoresistance to CDDP and metastasis by targeting inhibiting DNMT3B and induces stemness in gastric cancer
title_full miR-492 promotes chemoresistance to CDDP and metastasis by targeting inhibiting DNMT3B and induces stemness in gastric cancer
title_fullStr miR-492 promotes chemoresistance to CDDP and metastasis by targeting inhibiting DNMT3B and induces stemness in gastric cancer
title_full_unstemmed miR-492 promotes chemoresistance to CDDP and metastasis by targeting inhibiting DNMT3B and induces stemness in gastric cancer
title_short miR-492 promotes chemoresistance to CDDP and metastasis by targeting inhibiting DNMT3B and induces stemness in gastric cancer
title_sort mir-492 promotes chemoresistance to cddp and metastasis by targeting inhibiting dnmt3b and induces stemness in gastric cancer
topic Cancer
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064790/
https://www.ncbi.nlm.nih.gov/pubmed/32065219
http://dx.doi.org/10.1042/BSR20194342
work_keys_str_mv AT wushuai mir492promoteschemoresistancetocddpandmetastasisbytargetinginhibitingdnmt3bandinducesstemnessingastriccancer
AT xiejian mir492promoteschemoresistancetocddpandmetastasisbytargetinginhibitingdnmt3bandinducesstemnessingastriccancer
AT shihao mir492promoteschemoresistancetocddpandmetastasisbytargetinginhibitingdnmt3bandinducesstemnessingastriccancer
AT wangziwei mir492promoteschemoresistancetocddpandmetastasisbytargetinginhibitingdnmt3bandinducesstemnessingastriccancer