miR-153 promotes neural differentiation by activating the cell adhesion/Ca2+ signaling pathway and targeting ion channel activity in HT-22 cells by bioinformatic analysis

Li Jiao; Zhang Junfang; Li Yanna; Jin Caixia; Zhang Chen; Jia Song; Xu Jie; Yan Xiaoli; Gui Xin; Xing Libo; Wang Feng; Lu Lixia; Xu Chunli; Xu Lei

doi:10.1016/j.heliyon.2024.e30204

miR-153 promotes neural differentiation by activating the cell adhesion/Ca²⁺ signaling pathway and targeting ion channel activity in HT-22 cells by bioinformatic analysis

Heliyon. 2024 Apr 26;10(9):e30204. doi: 10.1016/j.heliyon.2024.e30204. eCollection 2024 May 15.

Authors

Li Jiao¹, Zhang Junfang¹, Li Yanna¹, Jin Caixia², Zhang Chen³, Jia Song¹, Xu Jie¹, Yan Xiaoli¹, Gui Xin⁴, Xing Libo⁴, Wang Feng⁵, Lu Lixia², Xu Chunli⁵, Xu Lei²

Affiliations

¹ Teaching Laboratory Center, Tongji University School of Medicine, Shanghai, China.
² Department of Biochemistry and Molecular Biology, Tongji University School of Medicine, Shanghai, China.
³ Department of Laboratory Research Center, Tongji University School of Medicine, Shanghai, China.
⁴ School of Life Science and Technology, Tongji University, Shanghai, China.
⁵ Department of Neurology, The Seventh People's Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Abstract

MicroRNAs have been studied extensively in neurodegenerative diseases. In a previous study, miR-153 promoted neural differentiation and projection formation in mouse hippocampal HT-22 cells. However, the pathways and molecular mechanism underlying miR-153-induced neural differentiation remain unclear. To explore the molecular mechanism of miR-153 on neural differentiation, we performed RNA sequencing on miR-153-overexpressed HT-22 cells. Based on RNA sequencing, differentially expressed genes (DEGs) and pathways in miR-153-overexpressed cells were identified. The Database for Annotation, Visualization and Integrated Discovery and Gene Set Enrichment Analysis were used to perform functional annotation and enrichment analysis of DEGs. Targetscan predicted the targets of miR-153. The Search Tool for the Retrieval of Interacting Genes and Cytoscape, were used to construct protein-protein interaction networks and identify hub genes. Q-PCR was used to detect mRNA expression of the identified genes. The expression profiles of the identified genes were compared between embryonic days 9.5 (E9.5) and E11.5 in the embryotic mouse brain of the GDS3442 dataset. Cell Counting Kit-8 assay was used to determine cell proliferation and cellular susceptibility to amyloid β-protein (Aβ) toxicity in miR-153-overexpressed cells. The results indicated that miR-153 increased cell adhesion/Ca²⁺ (Cdh5, Nrcam, and P2rx4) and Bdnf/Ntrk2 neurotrophic signaling pathway, and decreased ion channel activity (Kcnc3, Kcna4, Clcn5, and Scn5a). The changes in the expression of the identified genes in miR-153-overexpressed cells were consistent with the expression profile of GDS3442 during neural differentiation. In addition, miR-153 overexpression decreased cellular susceptibility to Aβ toxicity in HT-22 cells. In conclusion, miR-153 overexpression may promote neural differentiation by inducing cell adhesion and the Bdnf/Ntrk2 pathway, and regulating electrophysiological maturity by targeting ion channels. MiR-153 may play an important role in neural differentiation; the findings provide a useful therapeutic direction for neurodegenerative diseases.

Keywords: Bioinformatic analysis; Ion channel; Neural cell adhesion; Neural differentiation; Receptor tyrosine kinase; miR-153.