Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma - Peiminine Interferes with This Interaction

Sep 24, 2026

Uploaded by Patrick

Glioblastoma (GBM) is an aggressive, incurable primary brain tumor with limited patient survival, making molecular mechanism research crucial for effective therapies. The study cloned and sequenced an alternatively spliced HSD11B1L variant (HSD11B1L-181) that is specifically expressed in GBM cells. Overexpression promotes GBM cell proliferation, migration, and invasion, while knockdown suppresses oncogenic potential. Parkin directly interacts with HSD11B1L-181, and peiminine blocks this interaction, reducing carcinogenesis in cellular, ectopic, and orthotopic xenograft mouse models.

LanguageEnglish

CategoryHealthcare

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Introduction

Alternative splicing overview

GBM and abnormal alternative splicing

cells Article Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction Ru-Huei Fu 1,2, *,†, Syuan-Yu Hong 1,3,4,†, Chia-Wen Tsai 5, Shih-Ping Liu 1,2, Shao-Chih Chiu 1, Meng-Zhen Wu 1, Woei-Cherng Shyu 1,2 and Shinn-Zong Lin 6,7 Citation: Fu, R.-H.; Hong, S.-Y.; Tsai, C.-W.; Liu, S.-P.; Chiu, S.-C.; Wu, M.-Z.; Shyu, W.-C.; Lin, S.-Z. Interaction of a Novel Alternatively Spliced Variant of HSD11B1L with Parkin Enhances the Carcinogenesis Potential of Glioblastoma: Peiminine Interferes with This Interaction. Cells 2023, 12, 894. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/cells12060894](10.3390/cells12060894) Academic Editor: Pablo Mart½n-Vasallo Received: 3 February 2023 Revised: 6 March 2023 Accepted: 10 March 2023 Published: 14 March 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan 2 Translational Medicine Research Center, China Medical University Hospital, Taichung 40447, Taiwan 3 Department of Medicine, School of Medicine, China Medical University, Taichung 40447, Taiwan 4 Division of Pediatric Neurology, China Medical University Children's Hospital, Taichung 40447, Taiwan 5 Department of Nutrition, China Medical University, Taichung 40402, Taiwan 6 Buddhist Tzu Chi Bioinnovation Center, Tzu Chi Foundation, Hualien 97002, Taiwan 7 Department of Neurosurgery, Buddhist Tzu Chi General Hospital, Hualien 97002, Taiwan * Correspondence: [rhfu@mail.cmu.edu.tw](rhfu@mail.cmu.edu.tw); Tel.: +886-4-22052121 (ext. 7826)† These authors contributed equally to this work. Abstract: Glioblastoma (GBM) is a primary brain tumor of unknown etiology. It is extremely aggressive, incurable and has a short average survival time for patients. Therefore, understanding the precise molecular mechanisms of this diseases is essential to establish effective treatments. In this study, we cloned and sequenced a splice variant of the hydroxysteroid 11-􀀌 dehydrogenase 1 like gene (HSD11B1L) and named it HSD11B1L-181 . HSD11 B1L-181 was speciﬁcally expressed only in GBM cells. Overexpression of this variant can signiﬁcantly promote the proliferation, migration and invasion of GBM cells. Knockdown of HSD11B1L-181 expression inhibited the oncogenic potential of GBM cells. Furthermore, we identiﬁed the direct interaction of parkin with HSD11B1L-181 by screening the GBM cDNA expression library via yeast two-hybrid. Parkin is an RBR E3 ubiquitin ligase whose mutations are associated with tumorigenesis. Small interfering RNA treatment of parkin enhanced the proliferative, migratory and invasive abilities of GBM. Finally, we found that the alkaloid peiminine from the bulbs of Fritillaria thunbergii Miq blocks the interaction between HSD11B1L-181 and parkin, thereby lessening carcinogenesis of GBM. We further conﬁrmed the potential of peiminine to prevent GBM in cellular, ectopic and orthotopic xenograft mouse models. Taken together, these ﬁndings not only provide insight into GBM, but also present an opportunity for future GBM treatment. Keywords: glioblastoma; alternative splicing; hydroxysteroid 11-􀀌-dehydrogenase 1 like gene (HSD11B1L); proliferation; migration; invasion; parkin; peiminine 1. Introduction Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Almost 100% of patients relapse and the median survival time is less than tens of months. Due to its high invasiveness and heterogeneity, GBM is still extremely difﬁcult to relieve with

FAQs

What is HSD11B1L-181 and where is it expressed?

HSD11B1L-181 is an alternatively spliced variant of the HSD11B1L gene. It is specifically expressed in GBM cells.

How does HSD11B1L-181 affect glioblastoma cell behavior?

Overexpression significantly promotes GBM cell proliferation, migration, and invasion. Knockdown inhibits the oncogenic potential of GBM cells.

What role does the interaction between parkin and HSD11B1L-181 play, and how does peiminine affect it?

Parkin directly interacts with HSD11B1L-181, and parkin inhibition enhances GBM cell proliferative, migratory, and invasive abilities. Peiminine blocks the interaction, thereby lessening GBM carcinogenesis in multiple xenograft models.

Sep 24, 2026

Uploaded by Patrick