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BioImpacts. 2022;12: 195-202.
doi: 10.34172/bi.2021.22119
  Abstract View: 209
  PDF Download: 68

Original Research

Chitosan nanoparticle-mediated effect of antimiRNA-324-5p on decreasing the ovarian cancer cell proliferation by regulation of GLI1 expression

Ysrafil Ysrafil 1,2,3* ORCID logo, Indwiani Astuti 2 ORCID logo

1 Department of Pharmacy, Politeknik Kesehatan Kementerian Kesehatan Gorontalo, Gorontalo, Indonesia
2 Department of Pharmacology and Therapy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
3 Faculty of Medicine, Universitas Palangka Raya, Palangka Raya 73111, Indonesia
*Corresponding Author: Corresponding author: Ysrafil Ysrafil, Email: ysrafil@mail.ugm.ac.id

Abstract

Introduction: MicroRNAs (miRNAs) are short-sequence RNAs that regulate gene expression by targeting messenger RNAs (mRNAs). Recent studies reveal that miRNA-324-5p plays an important role in worsening the ovarian cancer prognosis when the expression is very high. This study aimed to develop a miRNA targeted therapy by targeting the miRNA-324-5p function as a miRNA-324-5p inhibitor.
Methods:
Chitosan nanoparticles were used for antimiRNA-324-5p delivery into SKOV3 cell lines formulated by ionic gelation method. Antiproliferative effect of CS-NPs-antimiRNA was assessed by the MTT Assay. A mechanism study assessed the anticancer effect of the formula. In silico analysis used miRTar.Human and StarmiRDB combined with Genecard to predict the target genes of antimiR. Hawkdock web server was used to analyze protein-protein interactions that were further validated by quantitative polymerase chain reaction (qPCR).
Results: The results of qPCR analysis showed endogenous miRNA-324-5p decreased after 24-hour transfection of antagonist miRNA. Furthermore, the MTT assay results showed that antimiRNA was able to inhibit SKOV3 cell proliferation (80 nM 68.13%, P<0.05). In silico analysis found miRNA-324-5p can regulate MEN1 and indirectly repress Gli1 mRNA. Validation results confirmed antimiR can decrease GLI1 mRNA expression.
Conclusion: Our results showed antimiRNA-324-5p can act as a microRNA-based therapy to inhibit ovarian cancer proliferation by the reduction of GLI1 expression.
Keywords: AntimiRNA-324-5p, SKOV3, Ovarian cancer, GLI1, Chitosan nanoparticle
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Submitted: 06 May 2020
Revision: 17 Jul 2020
Accepted: 22 Jul 2020
ePublished: 29 Nov 2021
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