Dataset Information

HES1 induces ITPR1-mediated autophagy to exert anti-metastatic effects in pituitary adenomas.

ABSTRACT:

Background

Pituitary adenomas (PAs) are prevalent intracranial tumors necessitating a comprehensive exploration of their molecular intricacies. This study delved into the molecular interactions among HES1 (hairy and enhancer of split 1), ITPR1 (inositol 1,4,5-trisphosphate receptor, type 1), and autophagy to elucidate their contributions to PA progression.

Methods

Our in-depth bioinformatics analysis identified ITPR1 as a central hub gene in the PA-associated dataset. It exhibited reduced expression in PA and held significant clinical diagnostic relevance. Motivated by this discovery, we investigated the consequences of ITPR1 overexpression, as well as the use of autophagy inhibitors 3-Methyladenine (3-MA) and Baf A1, while considering the transcriptional influence of HES1.

Results

In vitro experiments utilizing PA cell lines revealed that ITPR1 overexpression significantly hindered tumorigenic activities. In contrast, both 3-MA and Baf A1 exacerbated these tumorigenic properties, confirmed by a decreased LC3 II/LC3 I ratio, indicative of autophagy inhibition. Intriguingly, the concurrent introduction of ITPR1 and these inhibitors mitigated these intensified effects, implying a tumor-suppressive role for ITPR1. Further investigations pinpoint HES1 as a potential upstream regulator of ITPR1 transcription. Silencing HES1 lead to reduced ITPR1 promoter activity, weakening the impact of ITPR1 overexpression on autophagy. This neutralized the ITPR1-mediated suppressions on PA cell activities, including proliferation, invasion, and migration.

Conclusions

In summary, our research uncovered a complex regulatory interplay among HES1, ITPR1, and autophagy in the context of PA progression. These findings opened up promising avenues for novel therapeutic interventions targeting this intricate network to enhance PA treatment.

SUBMITTER: Qiu C

PROVIDER: S-EPMC10928634 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

<i>HES1</i> induces <i>ITPR1</i>-mediated autophagy to exert anti-metastatic effects in pituitary adenomas.

Qiu Chunjian C Yao Yao Y Hu Suqin S Xu Yixin Y

Translational cancer research 20240228 2

<h4>Background</h4>Pituitary adenomas (PAs) are prevalent intracranial tumors necessitating a comprehensive exploration of their molecular intricacies. This study delved into the molecular interactions among <i>HES1</i> (hairy and enhancer of split 1), <i>ITPR1</i> (inositol 1,4,5-trisphosphate receptor, type 1), and autophagy to elucidate their contributions to PA progression.<h4>Methods</h4>Our in-depth bioinformatics analysis identified <i>ITPR1</i> as a central hub gene in the PA-associated ...[more]

PMID: 38482414

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