Open Access

ARTICLE

CHRM3 is a novel prognostic factor of poor prognosis and promotes glioblastoma progression via activation of oncogenic invasive growth factors

BIN ZHANG^1,#, JIANYI ZHAO^3,#, YONGZHI WANG^2,#, HUA XU¹, BO GAO¹, GUANGNING ZHANG¹, BIN HAN¹, GUOHONG SONG¹, JUNCHEN ZHANG^1,*, WEI MENG^1,*

1 Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining, China
2 Department of Neurosurgery, The City Peoples’ Hospital of Fuyang, Fuyang, China
3 Brain Injury Center, Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

* Corresponding Authors: Junchen Zhang, ; Wei Meng,
# These authors contributed equally to this work

(This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)

Oncology Research 2023, 31(6), 917-927. https://doi.org/10.32604/or.2023.030425

Received 05 April 2023; Accepted 26 June 2023; Issue published 15 September 2023

Abstract

Glioblastoma (GBM) is the most aggressive cancer of the brain and has a high mortality rate due to the lack of effective treatment strategy. Clarification of molecular mechanisms of GBM’s characteristic invasive growth are urgently needed to improve the poor prognosis. Single-nuclear sequencing of primary and recurrent GBM samples revealed that levels of M3 muscarinic acetylcholine receptor (CHRM3) were significantly higher in the recurrent samples than in the primary samples. Moreover, immunohistochemical staining of an array of GBM samples showed that high levels of CHRM3 correlated with poor prognosis, consistent with The Cancer Genome Atlas database. Knockdown of CHRM3 inhibited GBM cell growth and invasion. An assay of orthotopic GBM animal model in vivo indicated that inhibition of CHRM3 significantly suppressed GBM progression with prolonged survival time. Transcriptome analysis revealed that CHRM3 knockdown significantly reduced an array of classic factors involved in cancer invasive growth, including MMP1/MMP3/MMP10/MMP12 and CXCL1/CXCL5/CXCL8. Taken together, CHRM3 is a novel and vital factor of GBM progression via regulation of multiple oncogenic genes and may serve as a new biomarker for prognosis and therapy of GBM patients.

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Keywords

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