# MiR-148a-3p/SIRT7 axis promotes glioma progression and regulates temozolomide chemosensitivity

## TL;DR

This study shows that the miR-148a-3p/SIRT7 pathway promotes glioma growth and affects how well temozolomide chemotherapy works.

## Contribution

The study identifies miR-148a-3p as a regulator of SIRT7, which influences glioma progression and temozolomide sensitivity.

## Key findings

- SIRT7 is overexpressed in glioma and linked to worse patient outcomes.
- Reducing SIRT7 or increasing miR-148a-3p inhibits glioma cell growth and induces apoptosis.
- SIRT7 knockdown enhances the effectiveness of temozolomide in glioma treatment.

## Abstract

Glioma is a highly malignant primary neoplasm of the central nervous system. Temozolomide (TMZ) is the first-line chemotherapeutic drug for glioma, commonly employed in conjunction with radiotherapy to improve overall patient outcomes, but the resistance significantly limits its efficacy. Identifying regulatory molecular targets that influence glioma progression and TMZ sensitivity is critical improve treatment outcomes. Even though SIRT7 has been implicated in tumorigenesis, the regulatory mechanisms of SIRT7 and the role of its upstream microRNAs in glioma progression remain unclear.

We constructed SIRT7 knockdown and overexpression in glioma cells lines, and detected the tumor phenotypes. Moreover, both in - vitro and in - vivo experiments were carried out to assess the influence of SIRT7 expression levels on the treatment effectiveness of temozolomide (TMZ) in glioma.

Our research indicated that SIRT7 is significantly over - expressed in tumor specimens obtained from glioma patients. This over - expression is associated with the tumor stage and a unfavorable prognosis. In addition, reducing the expression of SIRT7 can effectively impede the advancement of glioma cells. It has been confirmed that SIRT7 serves as a downstream target of miR-148a-3p. When there is an upregulation of miR-148a-3p, it suppresses the proliferation of glioma cells. Moreover, it causes tumor cells to become arrested in the G1 phase and stimulates cell death via apoptosis. Interestingly, SIRT7 knockdown enhanced TMZ-induced cytotoxicity in vitro and potentiated TMZ antitumor effects in glioblastoma xenografts.

The aforementioned results suggested the miR-148a-3p/SIRT7 axis drives glioma progression and modulates TMZ sensitivity, and targeting this axis may represent a promising therapeutic approach to overcome TMZ resistance in glioma.