Cargando…
KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis
BACKGROUND: Kinesin superfamily proteins (KIFs) can transport membranous organelles and protein complexes in an ATP-dependent manner. Kinesin family member 15 (KIF15) is overexpressed in various cancers. However, the function of KIF15 in gastric cancer (GC) is still unclear. METHODS: GC patients’ da...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160940/ https://www.ncbi.nlm.nih.gov/pubmed/32322172 http://dx.doi.org/10.1186/s12935-020-01199-7 |
_version_ | 1783522853480562688 |
---|---|
author | Ding, Lixian Li, Bin Yu, Xiaotong Li, Zhongsheng Li, Xinglong Dang, Shuwei Lv, Qiang Wei, Jiufeng Sun, Haixia Chen, Hongsheng Liu, Ming Li, Guodong |
author_facet | Ding, Lixian Li, Bin Yu, Xiaotong Li, Zhongsheng Li, Xinglong Dang, Shuwei Lv, Qiang Wei, Jiufeng Sun, Haixia Chen, Hongsheng Liu, Ming Li, Guodong |
author_sort | Ding, Lixian |
collection | PubMed |
description | BACKGROUND: Kinesin superfamily proteins (KIFs) can transport membranous organelles and protein complexes in an ATP-dependent manner. Kinesin family member 15 (KIF15) is overexpressed in various cancers. However, the function of KIF15 in gastric cancer (GC) is still unclear. METHODS: GC patients’ data from The Cancer Genome Atlas (TCGA) were analyzed by bioinformatics methods. The expression of KIF15 was examined in GC and paracarcinoma tissues from 41 patients to verify the analysis results. The relationship between KIF15 expression and clinical characteristics were also observed by bioinformatics methods. Kaplan–Meier survival analysis of 122 GC patients in our hospital was performed to explore the relationship between KIF15 expression levels and GC patients’ prognosis. KIF15 was downregulated in GC cell lines AGS and SGC-7901 by transfecting a lentivirus-mediated shRNA plasmid targeting KIF15. In vitro, GC cell proliferation and apoptosis were detected by MTT assay, colony formation assay, and Annexin V-APC staining. In vivo, xenograft experiments were used to verify the in vitro results. Furthermore, Human Apoptosis Antibody Array kit was used to screen possible targets of KIF15 in GC cell lines. RESULTS: The bioinformatics results showed that KIF15 expression levels were higher in GC tissues than in normal tissues. IHC showed same results. High expression of KIF15 was statistical correlated with high age and early histologic stage. Kaplan–Meier curves indicated that high KIF15 expression predict poor prognosis in patients with GC. MTT assay and colony formation assay showed that KIF15 promote GC cell proliferation. Annexin V-APC staining found that KIF15 can inhibit GC cell apoptosis. Xenograft experiments reveal that downregulating KIF15 can inhibit GC tumor growth and promote GC apoptosis. Through detection of 43 anti-apoptotic proteins by the Human Apoptosis Antibody Array kit, it was confirmed that knocking down KIF15 can reduce seven anti-apoptotic proteins expression. CONCLUSIONS: Taken together, our study revealed a critical role for KIF15 to inhibit GC cell apoptosis and promote GC cell proliferation. KIF15 may decrease anti-apoptotic proteins expression by regulating apoptosis pathways. High expression of KIF15 predicts a poor prognosis in patients with GC. KIF15 might be a novel prognostic biomarker and a therapeutic target for GC. |
format | Online Article Text |
id | pubmed-7160940 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-71609402020-04-22 KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis Ding, Lixian Li, Bin Yu, Xiaotong Li, Zhongsheng Li, Xinglong Dang, Shuwei Lv, Qiang Wei, Jiufeng Sun, Haixia Chen, Hongsheng Liu, Ming Li, Guodong Cancer Cell Int Primary Research BACKGROUND: Kinesin superfamily proteins (KIFs) can transport membranous organelles and protein complexes in an ATP-dependent manner. Kinesin family member 15 (KIF15) is overexpressed in various cancers. However, the function of KIF15 in gastric cancer (GC) is still unclear. METHODS: GC patients’ data from The Cancer Genome Atlas (TCGA) were analyzed by bioinformatics methods. The expression of KIF15 was examined in GC and paracarcinoma tissues from 41 patients to verify the analysis results. The relationship between KIF15 expression and clinical characteristics were also observed by bioinformatics methods. Kaplan–Meier survival analysis of 122 GC patients in our hospital was performed to explore the relationship between KIF15 expression levels and GC patients’ prognosis. KIF15 was downregulated in GC cell lines AGS and SGC-7901 by transfecting a lentivirus-mediated shRNA plasmid targeting KIF15. In vitro, GC cell proliferation and apoptosis were detected by MTT assay, colony formation assay, and Annexin V-APC staining. In vivo, xenograft experiments were used to verify the in vitro results. Furthermore, Human Apoptosis Antibody Array kit was used to screen possible targets of KIF15 in GC cell lines. RESULTS: The bioinformatics results showed that KIF15 expression levels were higher in GC tissues than in normal tissues. IHC showed same results. High expression of KIF15 was statistical correlated with high age and early histologic stage. Kaplan–Meier curves indicated that high KIF15 expression predict poor prognosis in patients with GC. MTT assay and colony formation assay showed that KIF15 promote GC cell proliferation. Annexin V-APC staining found that KIF15 can inhibit GC cell apoptosis. Xenograft experiments reveal that downregulating KIF15 can inhibit GC tumor growth and promote GC apoptosis. Through detection of 43 anti-apoptotic proteins by the Human Apoptosis Antibody Array kit, it was confirmed that knocking down KIF15 can reduce seven anti-apoptotic proteins expression. CONCLUSIONS: Taken together, our study revealed a critical role for KIF15 to inhibit GC cell apoptosis and promote GC cell proliferation. KIF15 may decrease anti-apoptotic proteins expression by regulating apoptosis pathways. High expression of KIF15 predicts a poor prognosis in patients with GC. KIF15 might be a novel prognostic biomarker and a therapeutic target for GC. BioMed Central 2020-04-15 /pmc/articles/PMC7160940/ /pubmed/32322172 http://dx.doi.org/10.1186/s12935-020-01199-7 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data. |
spellingShingle | Primary Research Ding, Lixian Li, Bin Yu, Xiaotong Li, Zhongsheng Li, Xinglong Dang, Shuwei Lv, Qiang Wei, Jiufeng Sun, Haixia Chen, Hongsheng Liu, Ming Li, Guodong KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis |
title | KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis |
title_full | KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis |
title_fullStr | KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis |
title_full_unstemmed | KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis |
title_short | KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis |
title_sort | kif15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160940/ https://www.ncbi.nlm.nih.gov/pubmed/32322172 http://dx.doi.org/10.1186/s12935-020-01199-7 |
work_keys_str_mv | AT dinglixian kif15facilitatesgastriccancerviaenhancingproliferationinhibitingapoptosisandpredictpoorprognosis AT libin kif15facilitatesgastriccancerviaenhancingproliferationinhibitingapoptosisandpredictpoorprognosis AT yuxiaotong kif15facilitatesgastriccancerviaenhancingproliferationinhibitingapoptosisandpredictpoorprognosis AT lizhongsheng kif15facilitatesgastriccancerviaenhancingproliferationinhibitingapoptosisandpredictpoorprognosis AT lixinglong kif15facilitatesgastriccancerviaenhancingproliferationinhibitingapoptosisandpredictpoorprognosis AT dangshuwei kif15facilitatesgastriccancerviaenhancingproliferationinhibitingapoptosisandpredictpoorprognosis AT lvqiang kif15facilitatesgastriccancerviaenhancingproliferationinhibitingapoptosisandpredictpoorprognosis AT weijiufeng kif15facilitatesgastriccancerviaenhancingproliferationinhibitingapoptosisandpredictpoorprognosis AT sunhaixia kif15facilitatesgastriccancerviaenhancingproliferationinhibitingapoptosisandpredictpoorprognosis AT chenhongsheng kif15facilitatesgastriccancerviaenhancingproliferationinhibitingapoptosisandpredictpoorprognosis AT liuming kif15facilitatesgastriccancerviaenhancingproliferationinhibitingapoptosisandpredictpoorprognosis AT liguodong kif15facilitatesgastriccancerviaenhancingproliferationinhibitingapoptosisandpredictpoorprognosis |