Theranostics 2022; 12(8):3847-3861. doi:10.7150/thno.71100 This issue Cite

Research Paper

PTBP1 knockdown promotes neural differentiation of glioblastoma cells through UNC5B receptor

Kankai Wang1,2, Sishi Pan1,2, Peiqi Zhao1,2, Li Liu3, Zhen Chen1,2, Han Bao1,2, Hao Wang1,2, Ying Zhang1,2, Qichuan Zhuge1,2✉, Jianjing Yang1,2✉

1. Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
2. Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
3. Zhejiang Provincial Key Laboratory of Interventional Pulmonology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.

Citation:
Wang K, Pan S, Zhao P, Liu L, Chen Z, Bao H, Wang H, Zhang Y, Zhuge Q, Yang J. PTBP1 knockdown promotes neural differentiation of glioblastoma cells through UNC5B receptor. Theranostics 2022; 12(8):3847-3861. doi:10.7150/thno.71100. https://www.thno.org/v12p3847.htm
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Abstract

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Rationale: Cell reprogramming technology is utilized to prevent cancer progression by transforming cells into terminally differentiated, non-proliferating states. Polypyrimidine tract binding protein 1 (PTBP1) is an RNA binding protein required for the growth of neurons and may directly transform multiple normal human cells into functioning neurons in vitro and in vivo when expressed at low levels. As a result, we identified it as a key to inhibiting cancer cell proliferation by boosting glioblastoma cell neural differentiation.

Methods: Immunocytofluorescence (ICF) targeting TUJ1, MAP2, KI67, and EdU were utilized to evaluate glioblastoma cell reprogramming under PTBP1 knockdown or other conditions. PTBP1 and other target genes were detected using Western blotting and qRT-PCR. Activating protein phosphatase 2A (PP2A) and RhoA were detected using specific kits. CCK8 assays were employed to detect cell viability. Bioluminescence, immunohistofluorescence (IHF), and Kaplan-Meier survival analyses were utilized to demonstrate the in vivo reprogramming efficiency of PTBP1 knockdown in U87 murine glioblastoma model. In this study, RNA-seq technology was used to examine the intrinsic pathway.

Results: The expression of TUJ1 and MAP2 neural markers, as well as the absence of KI67 and EdU proliferative markers in U251, U87, and KNS89 cells, indicated that glioblastoma cell reprogramming was successful. In vivo, U87 growth generated xenografts was substantially shrank due to PTBP1 knockdown induced neural differentiation, and these tumor-bearing mice had a prolonged survival time. Following RNA-seq, ten potential downstream genes were eliminated. Lentiviral interference and inhibitors blocking tests demonstrated that UNC5B receptor and its downstream signaling were essential in the neural differentiation process mediated by PTBP1 knockdown in glioblastoma cells.

Conclusions: Our results indicate that PTBP1 knockdown promotes neural differentiation of glioblastoma cells via UNC5B receptor, consequently suppressing cancer cell proliferation in vitro and in vivo, providing a promising and feasible approach for glioblastoma treatment.

Keywords: glioblastoma, cell reprogramming, PTBP1, proliferation, neural differentiation


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APA
Wang, K., Pan, S., Zhao, P., Liu, L., Chen, Z., Bao, H., Wang, H., Zhang, Y., Zhuge, Q., Yang, J. (2022). PTBP1 knockdown promotes neural differentiation of glioblastoma cells through UNC5B receptor. Theranostics, 12(8), 3847-3861. https://doi.org/10.7150/thno.71100.

ACS
Wang, K.; Pan, S.; Zhao, P.; Liu, L.; Chen, Z.; Bao, H.; Wang, H.; Zhang, Y.; Zhuge, Q.; Yang, J. PTBP1 knockdown promotes neural differentiation of glioblastoma cells through UNC5B receptor. Theranostics 2022, 12 (8), 3847-3861. DOI: 10.7150/thno.71100.

NLM
Wang K, Pan S, Zhao P, Liu L, Chen Z, Bao H, Wang H, Zhang Y, Zhuge Q, Yang J. PTBP1 knockdown promotes neural differentiation of glioblastoma cells through UNC5B receptor. Theranostics 2022; 12(8):3847-3861. doi:10.7150/thno.71100. https://www.thno.org/v12p3847.htm

CSE
Wang K, Pan S, Zhao P, Liu L, Chen Z, Bao H, Wang H, Zhang Y, Zhuge Q, Yang J. 2022. PTBP1 knockdown promotes neural differentiation of glioblastoma cells through UNC5B receptor. Theranostics. 12(8):3847-3861.

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