OLFML2A Downregulation Inhibits Glioma Proliferation Through Suppression of Wnt/β-Catenin Signaling

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

doi:10.3389/fonc.2021.717917

Frontiers in Oncology (Sep 2021)

OLFML2A Downregulation Inhibits Glioma Proliferation Through Suppression of Wnt/β-Catenin Signaling

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

Affiliations

Shize Ma: Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, China
Shize Ma: Second Clinical School, Lanzhou University, Lanzhou, China
Lei Duan: Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, China
Lei Duan: Second Clinical School, Lanzhou University, Lanzhou, China
Huateng Dong: Department of Pediatric Neurology, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou, China
Xiaodong Ma: Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, China
Xiaodong Ma: Second Clinical School, Lanzhou University, Lanzhou, China
Xinyu Guo: Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, China
Xinyu Guo: Second Clinical School, Lanzhou University, Lanzhou, China
Jianli Liu: Second Clinical School, Lanzhou University, Lanzhou, China
Jianli Liu: Department of Radiology, Lanzhou University Second Hospital, Lanzhou, China
Guoqiang Li: Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, China
Guoqiang Li: Second Clinical School, Lanzhou University, Lanzhou, China
Yue Yu: Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, China
Yue Yu: Second Clinical School, Lanzhou University, Lanzhou, China
Yanlong Xu: Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, China
Yanlong Xu: Second Clinical School, Lanzhou University, Lanzhou, China
Guoqiang Yuan: Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, China
Guoqiang Yuan: Second Clinical School, Lanzhou University, Lanzhou, China
Xingkun Zhao: Second Clinical School, Lanzhou University, Lanzhou, China
Guopeng Tian: Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, China
Guopeng Tian: Second Clinical School, Lanzhou University, Lanzhou, China
Shijia Zhai: Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, China
Shijia Zhai: Second Clinical School, Lanzhou University, Lanzhou, China
Yawen Pan: Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, China
Yawen Pan: Second Clinical School, Lanzhou University, Lanzhou, China
Yinian Zhang: Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, China
Yinian Zhang: Second Clinical School, Lanzhou University, Lanzhou, China

DOI: https://doi.org/10.3389/fonc.2021.717917
Journal volume & issue: Vol. 11

Abstract

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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.

Published in Frontiers in Oncology

ISSN: 2234-943X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.frontiersin.org/journals/oncology/

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