ORIGINAL RESEARCH article
Front. Cell. Neurosci.
Sec. Cellular Neuropathology
Silencing MALAT1 represses pathological progression, inflammation, and vascular smooth muscle cell phenotype switching by regulating the SEMA3C-mediated Smad pathway in intracranial aneurysms
Provisionally accepted
Junlong Kang1,2Wei Li3Xinjie Gao4,5Xinhua Tian2Wei Feng2Xiang Yao2Feng Wei2Luyue Chen2Hongjin Chen2Junjiang Tong2
E Chen2*
Yuxiang Gu1,4,5*- 1The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
- 2Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- 3The Third Hospital of Xiamen, Xiamen, China
- 4Huashan Hospital Fudan University, Shanghai, China
- 5Neurosurgical Institute of Fudan University, Shanghai, China
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Background: The crucial role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in regulating aneurysm formation, inflammation, and neural dysfunction has gradually been recognized. This study aimed to evaluate the effects of MALAT1 modification on pathological changes, inflammation, vascular smooth muscle cell (VSMC) phenotype switching, and the underlying mechanism in intracranial aneurysms (IAs). Methods: MALAT1-overexpressing (oeMALAT1), MALAT1 short hairpin (shMALAT1), and semaphorin 3C (SEMA3C)-overexpressing (oeSEMA3C) lentiviruses were transfected alone or in combination into basilar artery VSMCs originating from IA rats. These lentiviruses were then stereotactically injected into IA rats. Results: In vitro, the overexpression of MALAT1 inhibited cell proliferation while promoting cell apoptosis and invasion; the release of TNF-α, IL-1β, and IL-6; and the transformation of IA basilar artery VSMCs from the contractile type to the synthetic type. However, the silencing of MALAT1 had the opposite effect. The silencing of MALAT1 downregulated SEMA3C, and its silencing inactivated the Smad pathway. Furthermore, SEMA3C overexpression attenuated the effects of MALAT1 silencing on IA basilar artery VSMC proliferation, apoptosis, invasiveness, proinflammatory cytokines, phenotype switching, and Smad pathway inactivation. In vivo, silencing MALAT1 reduced the release of TNF-α, IL-1β, and IL-6, decreased pathological progression, inhibited VSMC synthetic type switching, and inactivated the Smad pathway in IA rats. However, the overexpression of SEMA3C reversed these effects. Conclusion: Silencing MALAT1 represses pathological progression, inflammation, and VSMC phenotype switching by regulating the SEMA3C-mediated Smad pathway in IA.
Keywords: Intracranial Aneurysm, MALAT1, semaphorin 3C, Smadpathway, vascular smooth muscle cells
Received: 16 Sep 2025; Accepted: 04 Feb 2026.
Copyright: © 2026 Kang, Li, Gao, Tian, Feng, Yao, Wei, Chen, Chen, Tong, Chen and Gu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
E Chen
Yuxiang Gu
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