# Silencing MALAT1 represses pathological progression, inflammation, and vascular smooth muscle cell phenotype switching by regulating the SEMA3C-mediated Smad pathway in intracranial aneurysms

## TL;DR

Silencing MALAT1 reduces aneurysm progression and inflammation by affecting the SEMA3C-mediated Smad pathway in vascular smooth muscle cells.

## Contribution

This study reveals a novel regulatory mechanism involving MALAT1 and SEMA3C in intracranial aneurysms.

## Key findings

- Silencing MALAT1 inhibits VSMC proliferation and inflammation while promoting apoptosis.
- SEMA3C overexpression reverses the effects of MALAT1 silencing in aneurysm models.
- MALAT1 silencing inactivates the Smad pathway and reduces aneurysm progression in rats.

## Abstract

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).

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.

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.

Silencing MALAT1 represses pathological progression, inflammation, and VSMC phenotype switching by regulating the SEMA3C-mediated Smad pathway in IA.