RNA Interference based Midkine Gene Therapy for Hepatocellular Carcinoma

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Mamdouh S.; Khorshed F.E.-Z.M.; Hammad G.; Magdy M.; Abdelraouf A.; Hemida E.; Shemis M.

Journal: Asian Pacific Journal of Cancer Prevention

Publisher: Asian Pacific Organization for Cancer Prevention

Publication Date: 1 July 2024

Volume / Issue: Volume 25 / Issue 7

Pages: 2371–2379

ISSN: 15137368

DOI: 10.31557/APJCP.2024.25.7.2371

Scopus: View on Scopus

PubMed: 39068570

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Mamdouh S., Biochemistry and Molecular Biology Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt; Khorshed F.E.-Z.M., Biochemistry and Molecular Biology Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt; Hammad G., Faculty of Biotechnology, October University for Modern Sciences & Arts (MSA), Giza, Egypt; Magdy M., Department of Pathology, Theodor Bilharz Research Institute, Cairo, Egypt; Abdelraouf A., Department of Hepatobiliopancreatic Surgery, National Hepatology and Tropical Medicine Research Institute, (NHTMRI), Cairo, Egypt; Hemida E., Fellow of Biochemistry, Obstetrics and Gynecology Hospital, Ain Shams University, Cairo, Egypt; Shemis M., Biochemistry and Molecular Biology Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt

Abstract

Background: Hepatocellular carcinoma (HCC) arises from hepatocytes and accounts for 90% of primary liver cancer. Reasons for HCC prognosis remaining dismal are that HCC is asymptomatic in its early stages, leading to late diagnosis, and it is markedly resistant to conventional chemo- and radiotherapy. In this study, we investigated RNA interference (RNAi)–based treatment for HCC by targeting MDK. Aim: The present study aimed to evaluate MDK serum levels as a diagnostic biomarker for HCC detection and the effect of MDK silencing by RNAi on HCC. Subjects and methods: A total of 140 participants, including 120 patients diagnosed with HCC and 20 healthy volunteers were enrolled in this study, all patients who underwent liver resection were sampled for tumor and adjacent non-tumor liver tissues, in addition to 5 ml of blood sample. Midkine expression levels were evaluated by ELISA and by qRT-PCR. The in vitro transfection and gene knockdown efficiency of midkine by MDK-siRNA was detected by qRT-PCR and ELISA. Gene knockdown effect at the molecule level on the proliferation of HepG2 in vitro was determined by cell counting. Results: The results showed that the expression of MDK was significantly increased in the serum of HCC patients compared to control serum samples with P<0.001 and significant elevated expression levels of MDK in tumor tissues compared to non-tumor ones with P<0.001. It also showed that down-regulation of MDK using RNAi can significantly inhibit HepG2 cells. Conclusion: Molecular targeting of MDK using RNAi interference decreases proliferation and could be a therapeutic target. © (2024), (Asian Pacific Organization for Cancer Prevention). All rights reserved.

Keywords

gene therapy; HCC; Midkine; RNAi; Adult; Biomarkers, Tumor; Carcinoma, Hepatocellular; Case-Control Studies; Cell Proliferation; Female; Follow-Up Studies; Genetic Therapy; Hep G2 Cells; Humans; Liver Neoplasms; Male; Middle Aged; Prognosis; RNA Interference; RNA, Small Interfering; Tumor Cells, Cultured; MDK protein, human; small interfering RNA; tumor marker; blood; case control study; follow up; genetics; Hep-G2 cell line; human; liver cell carcinoma; liver tumor; pathology; procedures; therapy; tumor cell culture

Citation Information

Scopus Citations: 2

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