AEG-1 as a Novel Therapeutic Target in Colon Cancer: A Study from Silencing AEG-1 in BALB/c Mice to Large Data Analysis

  • Авторлар: Sriramulu S.1, Malayaperumal S.1, Banerjee A.1, Anbalagan M.2, Kumar M.1, Radha R.3, Liu X.4, Zhang H.5, Hu G.6, Sun X.7, Pathak S.1
  • Мекемелер:
    1. Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI)
    2. Department of Structural and Cellular Biology, Tulane University School of Medicine
    3. Department of Pathology, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI
    4. Center for Systems Biology, Department of Bioinformatics, School of Basic Medicine and Biological Sciences
    5. School of Medicine, Institute of Medical Sciences, Orebro University
    6. School of Medicine, Institute of Medical Sciences, Orebro University,
    7. Department of Oncology and Department of Biomedical and Clinical Sciences, Linköping University
  • Шығарылым: Том 24, № 4 (2024)
  • Беттер: 307-320
  • Бөлім: Life Sciences
  • URL: https://transsyst.ru/1566-5232/article/view/644031
  • DOI: https://doi.org/10.2174/0115665232273077240104045022
  • ID: 644031

Дәйексөз келтіру

Толық мәтін

Аннотация

Background:Astrocyte elevated gene-1 (AEG-1) is overexpressed in various malignancies. Exostosin-1 (EXT-1), a tumor suppressor, is an intermediate for malignant tumors. Understanding the mechanism behind the interaction between AEG-1 and EXT-1 may provide insights into colon cancer metastasis.

Methods:AOM/DSS was used to induce tumor in BALB/c mice. Using an in vivo-jetPEI transfection reagent, transient transfection of AEG-1 and EXT-1 siRNAs were achieved. Histological scoring, immunohistochemical staining, and gene expression studies were performed from excised tissues. Data from the Cancer Genomic Atlas and GEO databases were obtained to identify the expression status of AEG-1 and itsassociation with the survival.

Results:In BALB/c mice, the AOM+DSS treated mice developed necrotic, inflammatory and dysplastic changes in the colon with definite clinical symptoms such as loss of goblet cells, colon shortening, and collagen deposition. Administration of AEG-1 siRNA resulted in a substantial decrease in the disease activity index. Mice treated with EXT-1 siRNA showed diffusely reduced goblet cells. In vivo investigations revealed that PTCH-1 activity was influenced by upstream gene AEG-1, which in turn may affect EXT-1 activity. Data from The Cancer Genomic Atlas and GEO databases confirmed the upregulation of AEG-1 and downregulation of EXT-1 in cancer patients.

Conclusions:This study revealed that AEG-1 silencing might alter EXT-1 expression indirectly through PTCH-1, influencing cell-ECM interactions, and decreasing dysplastic changes, proliferation and invasion.

Негізгі сөздер

Авторлар туралы

Sushmitha Sriramulu

Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI)

Email: info@benthamscience.net

Sarubala Malayaperumal

Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI)

Email: info@benthamscience.net

Antara Banerjee

Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI)

Email: info@benthamscience.net

Muralidharan Anbalagan

Department of Structural and Cellular Biology, Tulane University School of Medicine

Email: info@benthamscience.net

Makalakshmi Kumar

Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI)

Email: info@benthamscience.net

Rajesh Radha

Department of Pathology, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI

Email: info@benthamscience.net

Xingyi Liu

Center for Systems Biology, Department of Bioinformatics, School of Basic Medicine and Biological Sciences

Email: info@benthamscience.net

Hong Zhang

School of Medicine, Institute of Medical Sciences, Orebro University

Email: info@benthamscience.net

Guang Hu

School of Medicine, Institute of Medical Sciences, Orebro University,

Email: info@benthamscience.net

Xiao-Feng Sun

Department of Oncology and Department of Biomedical and Clinical Sciences, Linköping University

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Surajit Pathak

Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI)

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

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