Exploring the Therapeutic Potential of TROP2 Gene Silencing in Hepatocellular Carcinoma

Fatma Yakoub; Hanem Hassan; Samah Mamdouh; Tarek Aboushousha; Fatma B Rashidi; Mohamed A El-Desouky

doi:10.2174/0118722083352578241225130252

Exploring the Therapeutic Potential of TROP2 Gene Silencing in Hepatocellular Carcinoma

Recent Pat Biotechnol. 2025 Jan 17. doi: 10.2174/0118722083352578241225130252. Online ahead of print.

Authors

Fatma Yakoub¹, Hanem Hassan², Samah Mamdouh², Tarek Aboushousha³, Fatma B Rashidi⁴, Mohamed A El-Desouky⁵

Affiliations

¹ Specialist, Biochemistry and Molecular Biology Department, Theodor Bilharz Research Institute, Giza, Egypt.
² Professor, Biochemistry and Molecular Biology Department, Theodor Bilharz Research Institute, Giza, Egypt.
³ Professor of pathology, Theodor Bilharz Research Institute, Giza, Egypt.
⁴ Professor Biochemistry Division, Chemistry Department, Faculty of Science, Giza, Cairo University, Egypt.
⁵ Professor Biochemistry Division, Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt.

PMID: 39835546
DOI: 10.2174/0118722083352578241225130252

Abstract

Background: Trophoblast Cell Surface Antigen 2 (Trop2) is a transmembrane glycoprotein that has been implicated in the progression and metastasis of various cancers, including hepatocellular carcinoma (HCC). Targeting Trop2 expression may represent a promising approach for the development of novel therapeutic strategies.

Objectives: This study aimed to investigate the effects of Trop2 knockdown using small interfering RNA (siRNA) on the phenotypic and molecular characteristics of the HepG2 liver cancer cell line.

Methods: HepG2 cells were transfected with different concentrations of Trop2-targeting siRNA (3 nM, 5 nM, and 7 nM) at various time intervals (6, 24, and 48 hrs). The expression of Trop2 was assessed by real-time PCR before and after transfection. The impact of Trop2 knockdown on cell apoptosis, migration, morphology, histopathological features, wound-healing assays, and microscopic analysis was examined. Additionally, the expression of the TPM1 gene was evaluated using immunohistochemical analysis.

Results: Trop2 mRNA level was significantly decreased in HepG2 cells in a time- and concentration-dependent manner following siRNA transfection. The downregulation of Trop2 resulted in a marked increase in apoptosis, a reduction in cell migration, and alterations in cell morphology and histopathological characteristics. Furthermore, the expression of the TPM1 gene was found to be upregulated in Trop2-knockdown HepG2 cells.

Conclusion: These results highlight the potential of Trop2 as a therapeutic target for the management of hepatocellular carcinoma.

Keywords: Hepatocellular Carcinoma; TPM1; Trop2; knockdown.; siRNA.