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RNA Interference based Midkine Gene Therapy for Hepatocellular Carcinoma.
- Source :
-
Asian Pacific journal of cancer prevention : APJCP [Asian Pac J Cancer Prev] 2024 Jul 01; Vol. 25 (7), pp. 2371-2379. Date of Electronic Publication: 2024 Jul 01. - Publication Year :
- 2024
-
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.<br />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.<br />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.<br />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.<br />Conclusion: Molecular targeting of MDK using RNAi interference decreases proliferation and could be a therapeutic target.
- Subjects :
- Humans
Male
Female
Middle Aged
Prognosis
RNA Interference
Genetic Therapy methods
Case-Control Studies
RNA, Small Interfering genetics
Hep G2 Cells
Follow-Up Studies
Adult
Tumor Cells, Cultured
Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular therapy
Carcinoma, Hepatocellular pathology
Liver Neoplasms genetics
Liver Neoplasms therapy
Liver Neoplasms pathology
Midkine genetics
Cell Proliferation
Biomarkers, Tumor genetics
Biomarkers, Tumor blood
Subjects
Details
- Language :
- English
- ISSN :
- 2476-762X
- Volume :
- 25
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Asian Pacific journal of cancer prevention : APJCP
- Publication Type :
- Academic Journal
- Accession number :
- 39068570
- Full Text :
- https://doi.org/10.31557/APJCP.2024.25.7.2371