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Original Article

Experimental Neurobiology 2019; 28(5): 628-641

Published online October 31, 2019

https://doi.org/10.5607/en.2019.28.5.628

© The Korean Society for Brain and Neural Sciences

LGR5 and Downstream Intracellular Signaling Proteins Play Critical Roles in the Cell Proliferation of Neuroblastoma, Meningioma and Pituitary Adenoma

Mina Hwang1†, Myung-Hoon Han2†, Hyun-Hee Park1*, Hojin Choi1, Kyu-Yong Lee1, Young Joo Lee1, Jae Min Kim2, Jin Hwan Cheong2, Je Il Ryu2, Kyueng-Whan Min3, Young-Ha Oh3, Yong Ko4 and Seong-Ho Koh1,5*

Departments of 1Neurology, 2Neurosurgery, and 3Pathology, Hanyang University Guri Hospital, Guri 11923, 4Department of Neurosurgery, Hanyang University Medical Center, Seoul 04763, 5Department of Translational Medicine, Hanyang University Graduate School of Biomedical Science & Engineering, Seoul 04763, Korea

Correspondence to: Seong-Ho Koh, TEL: 82-31-560-2260, FAX: 82-31-560-2267
e-mail: ksh213@hanyang.ac.kr
Hyun-Hee Park, TEL: 82-31-560-2260, FAX: 82-31-560-2267
e-mail: newdiaz@hanmail.net
These authors contributed equally to the work.

Received: May 31, 2019; Revised: September 9, 2019; Accepted: September 19, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License
(http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and
reproduction in any medium, provided the original work is properly cited.

Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) has been reported to play critical roles in the proliferation of various cancer cells. However, the roles of LGR5 in brain tumors and the specific intracellular signaling proteins directly associated with it remain unknown. Expression of LGR5 was first measured in normal brain tissue, meningioma, and pituitary adenoma of humans. To identify the downstream signaling pathways of LGR5, siRNA-mediated knockdown of LGR5 was performed in SH-SY5Y neuroblastoma cells followed by proteomics analysis with 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE). In addition, the expression of LGR5-associated proteins was evaluated in LGR5-inhibited neuroblastoma cells and in human normal brain, meningioma, and pituitary adenoma tissue. Proteomics analysis showed 12 protein spots were significantly different in expression level (more than two-fold change) and subsequently identified by peptide mass fingerprinting. A protein association network was constructed from the 12 identified proteins altered by LGR5 knockdown. Direct and indirect interactions were identified among the 12 proteins. HSP 90-beta was one of the proteins whose expression was altered by LGR5 knockdown. Likewise, we observed decreased expression of proteins in the hnRNP subfamily following LGR5 knockdown. In addition, we have for the first time identified significantly higher hnRNP family expression in meningioma and pituitary adenoma compared to normal brain tissue. Taken together, LGR5 and its downstream signaling play critical roles in neuroblastoma and brain tumors such as meningioma and pituitary adenoma.

Graphical Abstract


Keywords: LGR5, Neuroblastoma, Meningioma, Pituitary adenoma, hnRNP