EXOSC5 as a Novel Prognostic Marker Promotes Proliferation of Colorectal Cancer via Activating the ERK and AKT Pathways

Background and Objective: Exosome component 5 (EXOSC5) is a novel cancer-related gene that is aberrantly expressed in various malignances. However, the molecular mechanism and biological role of EXOSC5 have not been explored in colorectal cancer (CRC). In this study, we investigated the functions an...

Full description

Bibliographic Details
Main Authors: Hongda Pan, Jingxin Pan, Shibo Song, Lei Ji, Hong Lv, Zhangru Yang
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-07-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fonc.2019.00643/full
_version_ 1818265204669022208
author Hongda Pan
Hongda Pan
Hongda Pan
Hongda Pan
Jingxin Pan
Shibo Song
Lei Ji
Lei Ji
Hong Lv
Hong Lv
Zhangru Yang
Zhangru Yang
author_facet Hongda Pan
Hongda Pan
Hongda Pan
Hongda Pan
Jingxin Pan
Shibo Song
Lei Ji
Lei Ji
Hong Lv
Hong Lv
Zhangru Yang
Zhangru Yang
author_sort Hongda Pan
collection DOAJ
description Background and Objective: Exosome component 5 (EXOSC5) is a novel cancer-related gene that is aberrantly expressed in various malignances. However, the molecular mechanism and biological role of EXOSC5 have not been explored in colorectal cancer (CRC). In this study, we investigated the functions and mechanisms by which EXOSC5 promotes the progression of CRC.Methods: EXOSC5 expressions in CRC cell lines and paired CRC and adjacent normal tissues were measured via quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry (IHC). In vitro experiments including colony formation, Cell Counting Kit-8 (CCK-8), and flow cytometry and in vivo tumorigenesis assay were performed to explore the effects of EXOSC5 on growth of CRC. The impacts of EXOSC5 on ERK and Akt signaling pathways were measured by Western blot.Results: The mRNA and protein expression levels of EXOSC5 were up-regulated in CRC as compared to adjacent normal tissues. IHC analysis indicated that high EXOSC5 level was positively associated with poor prognosis. EXOSC5 overexpression facilitated the growth of CRC cells, while EXOSC5 knockdown led to decreased proliferation, G1/S phase transition arrest. The oncogenic functions of EXOSC5 were associated with activation of the ERK and Akt pathways in CRC.Conclusion: EXOSC5 is overexpressed in CRC and promotes CRC growth partly through activation of ERK and Akt signaling pathways. Accordingly, EXOSC5 may be a novel oncogene, and acts as a therapeutic target, or prognostic factor for CRC.
first_indexed 2024-12-12T19:47:06Z
format Article
id doaj.art-7d5a446bc06548fab55f9ae1d5ccf583
institution Directory Open Access Journal
issn 2234-943X
language English
last_indexed 2024-12-12T19:47:06Z
publishDate 2019-07-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Oncology
spelling doaj.art-7d5a446bc06548fab55f9ae1d5ccf5832022-12-22T00:14:04ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-07-01910.3389/fonc.2019.00643465040EXOSC5 as a Novel Prognostic Marker Promotes Proliferation of Colorectal Cancer via Activating the ERK and AKT PathwaysHongda Pan0Hongda Pan1Hongda Pan2Hongda Pan3Jingxin Pan4Shibo Song5Lei Ji6Lei Ji7Hong Lv8Hong Lv9Zhangru Yang10Zhangru Yang11Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, ChinaDepartment of Hematology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Gastrointestinal Surgery, Beijing Hospital, Beijing, ChinaDepartment of Hematology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, ChinaDepartment of Gastrointestinal Surgery, Beijing Hospital, Beijing, ChinaDepartment of Gastric Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Gastric Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Gastric Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaBackground and Objective: Exosome component 5 (EXOSC5) is a novel cancer-related gene that is aberrantly expressed in various malignances. However, the molecular mechanism and biological role of EXOSC5 have not been explored in colorectal cancer (CRC). In this study, we investigated the functions and mechanisms by which EXOSC5 promotes the progression of CRC.Methods: EXOSC5 expressions in CRC cell lines and paired CRC and adjacent normal tissues were measured via quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry (IHC). In vitro experiments including colony formation, Cell Counting Kit-8 (CCK-8), and flow cytometry and in vivo tumorigenesis assay were performed to explore the effects of EXOSC5 on growth of CRC. The impacts of EXOSC5 on ERK and Akt signaling pathways were measured by Western blot.Results: The mRNA and protein expression levels of EXOSC5 were up-regulated in CRC as compared to adjacent normal tissues. IHC analysis indicated that high EXOSC5 level was positively associated with poor prognosis. EXOSC5 overexpression facilitated the growth of CRC cells, while EXOSC5 knockdown led to decreased proliferation, G1/S phase transition arrest. The oncogenic functions of EXOSC5 were associated with activation of the ERK and Akt pathways in CRC.Conclusion: EXOSC5 is overexpressed in CRC and promotes CRC growth partly through activation of ERK and Akt signaling pathways. Accordingly, EXOSC5 may be a novel oncogene, and acts as a therapeutic target, or prognostic factor for CRC.https://www.frontiersin.org/article/10.3389/fonc.2019.00643/fullEXOSC5proliferationcolorectal cancerAkt signaling pathwayERK signaling pathwayprognosis
spellingShingle Hongda Pan
Hongda Pan
Hongda Pan
Hongda Pan
Jingxin Pan
Shibo Song
Lei Ji
Lei Ji
Hong Lv
Hong Lv
Zhangru Yang
Zhangru Yang
EXOSC5 as a Novel Prognostic Marker Promotes Proliferation of Colorectal Cancer via Activating the ERK and AKT Pathways
Frontiers in Oncology
EXOSC5
proliferation
colorectal cancer
Akt signaling pathway
ERK signaling pathway
prognosis
title EXOSC5 as a Novel Prognostic Marker Promotes Proliferation of Colorectal Cancer via Activating the ERK and AKT Pathways
title_full EXOSC5 as a Novel Prognostic Marker Promotes Proliferation of Colorectal Cancer via Activating the ERK and AKT Pathways
title_fullStr EXOSC5 as a Novel Prognostic Marker Promotes Proliferation of Colorectal Cancer via Activating the ERK and AKT Pathways
title_full_unstemmed EXOSC5 as a Novel Prognostic Marker Promotes Proliferation of Colorectal Cancer via Activating the ERK and AKT Pathways
title_short EXOSC5 as a Novel Prognostic Marker Promotes Proliferation of Colorectal Cancer via Activating the ERK and AKT Pathways
title_sort exosc5 as a novel prognostic marker promotes proliferation of colorectal cancer via activating the erk and akt pathways
topic EXOSC5
proliferation
colorectal cancer
Akt signaling pathway
ERK signaling pathway
prognosis
url https://www.frontiersin.org/article/10.3389/fonc.2019.00643/full
work_keys_str_mv AT hongdapan exosc5asanovelprognosticmarkerpromotesproliferationofcolorectalcancerviaactivatingtheerkandaktpathways
AT hongdapan exosc5asanovelprognosticmarkerpromotesproliferationofcolorectalcancerviaactivatingtheerkandaktpathways
AT hongdapan exosc5asanovelprognosticmarkerpromotesproliferationofcolorectalcancerviaactivatingtheerkandaktpathways
AT hongdapan exosc5asanovelprognosticmarkerpromotesproliferationofcolorectalcancerviaactivatingtheerkandaktpathways
AT jingxinpan exosc5asanovelprognosticmarkerpromotesproliferationofcolorectalcancerviaactivatingtheerkandaktpathways
AT shibosong exosc5asanovelprognosticmarkerpromotesproliferationofcolorectalcancerviaactivatingtheerkandaktpathways
AT leiji exosc5asanovelprognosticmarkerpromotesproliferationofcolorectalcancerviaactivatingtheerkandaktpathways
AT leiji exosc5asanovelprognosticmarkerpromotesproliferationofcolorectalcancerviaactivatingtheerkandaktpathways
AT honglv exosc5asanovelprognosticmarkerpromotesproliferationofcolorectalcancerviaactivatingtheerkandaktpathways
AT honglv exosc5asanovelprognosticmarkerpromotesproliferationofcolorectalcancerviaactivatingtheerkandaktpathways
AT zhangruyang exosc5asanovelprognosticmarkerpromotesproliferationofcolorectalcancerviaactivatingtheerkandaktpathways
AT zhangruyang exosc5asanovelprognosticmarkerpromotesproliferationofcolorectalcancerviaactivatingtheerkandaktpathways