OLFML2A Downregulation Inhibits Glioma Proliferation Through Suppression of Wnt/β-Catenin Signaling
Glioma is a highly heterogeneous and lethal tumor with an extremely poor prognosis. Through analysis of TCGA data, we identified that OLFML2A is a key promotor of gliomagenesis. However, the molecular function of OLFML2A and its underlying mechanism of action in glioma remain unclear. In this study,...
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.717917/full |
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| author | Shize Ma Shize Ma Lei Duan Lei Duan Huateng Dong Xiaodong Ma Xiaodong Ma Xinyu Guo Xinyu Guo Jianli Liu Jianli Liu Guoqiang Li Guoqiang Li Yue Yu Yue Yu Yanlong Xu Yanlong Xu Guoqiang Yuan Guoqiang Yuan Xingkun Zhao Guopeng Tian Guopeng Tian Shijia Zhai Shijia Zhai Yawen Pan Yawen Pan Yinian Zhang Yinian Zhang |
| author_facet | Shize Ma Shize Ma Lei Duan Lei Duan Huateng Dong Xiaodong Ma Xiaodong Ma Xinyu Guo Xinyu Guo Jianli Liu Jianli Liu Guoqiang Li Guoqiang Li Yue Yu Yue Yu Yanlong Xu Yanlong Xu Guoqiang Yuan Guoqiang Yuan Xingkun Zhao Guopeng Tian Guopeng Tian Shijia Zhai Shijia Zhai Yawen Pan Yawen Pan Yinian Zhang Yinian Zhang |
| author_sort | Shize Ma |
| collection | DOAJ |
| description | Glioma is a highly heterogeneous and lethal tumor with an extremely poor prognosis. Through analysis of TCGA data, we identified that OLFML2A is a key promotor of gliomagenesis. However, the molecular function of OLFML2A and its underlying mechanism of action in glioma remain unclear. In this study, we found that OLFML2A expression was significantly upregulated in glioma specimens and positively correlated with pathological grades in glioma patients. Moreover, Kaplan–Meier survival analysis of TCGA data revealed that glioma patients with higher OLFML2A expression had shorter overall survival. Importantly, OLFML2A knockdown in glioma cells inhibited cell proliferation and promoted apoptosis. Mechanistically, OLFML2A downregulation inhibits Wnt/β-catenin signaling by upregulating amyloid precursor protein (APP) expression and reducing stabilized β-catenin levels, leading to the repression of MYC, CD44, and CSKN2A2 expression. Furthermore, OLFML2A downregulation suppressed the growth of transplanted glioma subcutaneously and intracranially by inhibiting Wnt/β-catenin pathway-dependent cell proliferation. By uncovering the oncogenic effects in human and rodent gliomas, our data support OLFML2A as a potential therapeutic target for glioma. |
| first_indexed | 2024-12-24T03:54:26Z |
| format | Article |
| id | doaj.art-ef97f306f2ae4d419f4f5af71c742736 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-24T03:54:26Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-ef97f306f2ae4d419f4f5af71c7427362022-12-21T17:16:29ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-09-011110.3389/fonc.2021.717917717917OLFML2A Downregulation Inhibits Glioma Proliferation Through Suppression of Wnt/β-Catenin SignalingShize Ma0Shize Ma1Lei Duan2Lei Duan3Huateng Dong4Xiaodong Ma5Xiaodong Ma6Xinyu Guo7Xinyu Guo8Jianli Liu9Jianli Liu10Guoqiang Li11Guoqiang Li12Yue Yu13Yue Yu14Yanlong Xu15Yanlong Xu16Guoqiang Yuan17Guoqiang Yuan18Xingkun Zhao19Guopeng Tian20Guopeng Tian21Shijia Zhai22Shijia Zhai23Yawen Pan24Yawen Pan25Yinian Zhang26Yinian Zhang27Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, ChinaSecond Clinical School, Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, ChinaSecond Clinical School, Lanzhou University, Lanzhou, ChinaDepartment of Pediatric Neurology, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou, ChinaDepartment of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, ChinaSecond Clinical School, Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, ChinaSecond Clinical School, Lanzhou University, Lanzhou, ChinaSecond Clinical School, Lanzhou University, Lanzhou, ChinaDepartment of Radiology, Lanzhou University Second Hospital, Lanzhou, ChinaDepartment of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, ChinaSecond Clinical School, Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, ChinaSecond Clinical School, Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, ChinaSecond Clinical School, Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, ChinaSecond Clinical School, Lanzhou University, Lanzhou, ChinaSecond Clinical School, Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, ChinaSecond Clinical School, Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, ChinaSecond Clinical School, Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, ChinaSecond Clinical School, Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, ChinaSecond Clinical School, Lanzhou University, Lanzhou, ChinaGlioma is a highly heterogeneous and lethal tumor with an extremely poor prognosis. Through analysis of TCGA data, we identified that OLFML2A is a key promotor of gliomagenesis. However, the molecular function of OLFML2A and its underlying mechanism of action in glioma remain unclear. In this study, we found that OLFML2A expression was significantly upregulated in glioma specimens and positively correlated with pathological grades in glioma patients. Moreover, Kaplan–Meier survival analysis of TCGA data revealed that glioma patients with higher OLFML2A expression had shorter overall survival. Importantly, OLFML2A knockdown in glioma cells inhibited cell proliferation and promoted apoptosis. Mechanistically, OLFML2A downregulation inhibits Wnt/β-catenin signaling by upregulating amyloid precursor protein (APP) expression and reducing stabilized β-catenin levels, leading to the repression of MYC, CD44, and CSKN2A2 expression. Furthermore, OLFML2A downregulation suppressed the growth of transplanted glioma subcutaneously and intracranially by inhibiting Wnt/β-catenin pathway-dependent cell proliferation. By uncovering the oncogenic effects in human and rodent gliomas, our data support OLFML2A as a potential therapeutic target for glioma.https://www.frontiersin.org/articles/10.3389/fonc.2021.717917/fullolfactomedin-like 2A (OLFML2A)gliomaamyloid precursor protein (APP)proliferationapoptosisWnt/β-catenin signaling |
| spellingShingle | Shize Ma Shize Ma Lei Duan Lei Duan Huateng Dong Xiaodong Ma Xiaodong Ma Xinyu Guo Xinyu Guo Jianli Liu Jianli Liu Guoqiang Li Guoqiang Li Yue Yu Yue Yu Yanlong Xu Yanlong Xu Guoqiang Yuan Guoqiang Yuan Xingkun Zhao Guopeng Tian Guopeng Tian Shijia Zhai Shijia Zhai Yawen Pan Yawen Pan Yinian Zhang Yinian Zhang OLFML2A Downregulation Inhibits Glioma Proliferation Through Suppression of Wnt/β-Catenin Signaling Frontiers in Oncology olfactomedin-like 2A (OLFML2A) glioma amyloid precursor protein (APP) proliferation apoptosis Wnt/β-catenin signaling |
| title | OLFML2A Downregulation Inhibits Glioma Proliferation Through Suppression of Wnt/β-Catenin Signaling |
| title_full | OLFML2A Downregulation Inhibits Glioma Proliferation Through Suppression of Wnt/β-Catenin Signaling |
| title_fullStr | OLFML2A Downregulation Inhibits Glioma Proliferation Through Suppression of Wnt/β-Catenin Signaling |
| title_full_unstemmed | OLFML2A Downregulation Inhibits Glioma Proliferation Through Suppression of Wnt/β-Catenin Signaling |
| title_short | OLFML2A Downregulation Inhibits Glioma Proliferation Through Suppression of Wnt/β-Catenin Signaling |
| title_sort | olfml2a downregulation inhibits glioma proliferation through suppression of wnt β catenin signaling |
| topic | olfactomedin-like 2A (OLFML2A) glioma amyloid precursor protein (APP) proliferation apoptosis Wnt/β-catenin signaling |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.717917/full |
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