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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1529809
This article is part of the Research Topic Novel Molecular Targets in Cancer Therapy View all 9 articles

Unveiling the Role of ASPP1 in Cancer Progression: Pan-Cancer Bioinformatics and Experimental Validation in Colorectal Cancer

Provisionally accepted
Keyuan Xiao Keyuan Xiao 1Li Xiang Li Xiang 1Ihsan Ullah Ihsan Ullah 2Wenqing Hu Wenqing Hu 1Kaiqiang Wang Kaiqiang Wang 3Fan Yang Fan Yang 1Chengyu Yang Chengyu Yang 4Chunqi Feng Chunqi Feng 5Liang Zong Liang Zong 1Xinghua Li Xinghua Li 1*
  • 1 Changzhi People’s Hospital Affiliated to Changzhi Medical College, Changzhi, China
  • 2 School of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, Jilin Province, China
  • 3 Changzhi Medical College, Changzhi, Shanxi Province, China
  • 4 College of Life Sciences, Shanxi University, Taiyuan, Shanxi Province, China
  • 5 School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi Province, China

The final, formatted version of the article will be published soon.

    The Apoptosis-Stimulating Protein of P53 (ASPP) family contributes to apoptosis regulation and tumor suppression, with ASPP1 influencing processes like cancer cell proliferation, invasion, and migration. Its expression varies across cancer types, suggesting a potential role in oncogenesis. Methods: This study investigates ASPP1's role across various cancers using a comprehensive bioinformatics approach. Data were extracted from public resources, including The Cancer Genome Atlas (TCGA), GTEx, and the Human Protein Atlas, and analyzed via tools such as cBioPortal, GEPIA, and TIMER2. Statistical and network analyses were performed with R, Cytoscape, and Hiplot. ASPP1's function in colorectal cancer was further explored through in vitro assays, including qRT-PCR, Western blotting, colony formation, Transwell, and wound healing. Results: ASPP1 expression exhibited significant variability across different cancer types, with marked associations with patient outcomes, particularly overall survival (OS) and disease-specific survival (DSS) across several cancer types. In-depth protein-protein interaction (PPI) analysis revealed ASPP1's involvement in apoptosis and cancer progression networks. Functional enrichment analysis further linked ASPP1 to key apoptotic signaling pathways and transcriptional regulatory processes, underscoring its potential impact on tumor biology. Additionally, the expression of ASPP1 correlates with immune cell infiltration patterns, including cancer-associated fibroblasts and various immune markers, suggesting roles in immune response modulation. In vitro assays with colorectal cancer cell lines revealed significantly lower ASPP1 expression levels compared to normal colon cells (HCM460), and ASPP1 overexpression experiments showed a marked reduction in colorectal cancer cell proliferation, colony formation, invasion, and migration abilities. These cellular findings align with the bioinformatics predictions, highlighting ASPP1's role as a suppressor of metastatic traits in colorectal cancer.This study highlights ASPP1 as a forecasting biomarker in the colorectal cancers and potentially across other cancers. The findings support ASPP1's involvement in tumor biology, particularly regarding cell proliferation and metastatic potential, establishing a foundation for further investigation into its therapeutic relevance.

    Keywords: ASPP1, Pan-cancer analysis, tumor suppression, Immune Modulation, colorectal cancer Not applicable Xinghua Li: Writing -review & editing, project administration, Conceptualization. Keyuan Xiao: Validation, Writing -original draft

    Received: 17 Nov 2024; Accepted: 06 Dec 2024.

    Copyright: © 2024 Xiao, Xiang, Ullah, Hu, Wang, Yang, Yang, Feng, Zong and Li. 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: Xinghua Li, Changzhi People’s Hospital Affiliated to Changzhi Medical College, Changzhi, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.