MicroRNA-155-5p Diminishes in Vitro Ovarian Cancer Cell Viability by Targeting HIF1α Expression

Purpose: Ovarian cancer is the most lethal of gynecological malignancies. Recently, the development of microRNA (miRNA) -based therapeutics that could impact broad cellular programs, leading to inhibition of cancer cell viability, is gaining attention in the therapeutic landscape. The therapy is bas...

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Main Authors: Ysrafil Ysrafil, Indwiani Astuti, Sumadi Lukman Anwar, Ronny Martien, Firasti Agung Nugrahening Sumadi, Tirta Wardhana, Sofia Mubarika Haryana
Format: Article
Language:English
Published: Tabriz University of Medical Sciences 2020-08-01
Series:Advanced Pharmaceutical Bulletin
Subjects:
Online Access:https://apb.tbzmed.ac.ir/PDF/apb-10-630.pdf
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author Ysrafil Ysrafil
Indwiani Astuti
Sumadi Lukman Anwar
Ronny Martien
Firasti Agung Nugrahening Sumadi
Tirta Wardhana
Sofia Mubarika Haryana
author_facet Ysrafil Ysrafil
Indwiani Astuti
Sumadi Lukman Anwar
Ronny Martien
Firasti Agung Nugrahening Sumadi
Tirta Wardhana
Sofia Mubarika Haryana
author_sort Ysrafil Ysrafil
collection DOAJ
description Purpose: Ovarian cancer is the most lethal of gynecological malignancies. Recently, the development of microRNA (miRNA) -based therapeutics that could impact broad cellular programs, leading to inhibition of cancer cell viability, is gaining attention in the therapeutic landscape. The therapy is based on the presence of aberrant expressions of miRNA in cancer cells. Decreasing of tumor suppressor miRNA expression causes upregulation of oncoprotein, which worsens the prognosis of the ovarian cancer. Methods: miR-155-5p mimics were carried by chitosan nanoparticles using new nanotechnology methods. Cellular uptake of miRNA was assessed by fluorescence microscope while MTT and qPCR assay were used to determine miRNA profile and the effect of CS-NP/miRNA on SKOV3 cells. Results: Results of profiling validated using quantitative realtime-polymerase chain reaction (PCR) found one of the most altered tumor suppressor miRNAs, miR-155-5p was downregulated 892.15-fold. According to bioinformatic analysis we identified the miRNA could recognize and regulate HIF1α expression. Transfection of mimics for miR-155-5p showed significantly increased miR-155-5p endogen SKOV3 expression level compared to the control group. We found differences after transfection mimics for miR-155-5p 31.5 and 63 nanoMolar. Increasing of miR-155-5p endogen lead to diminished SKOV3 viability (by 30%; <0.05 at concentration 80 nanoMolar). These mimics may cause an increase in upregulated miR-155-5p endogen that can reduce HIF1α expression. Here we found 2-fold and 2.8-fold reduction of HIF1α expression level after transfection compared to the control group. Conclusion: According to these findings, the mimics miR-155-5p can inhibit ovarian cancer cell proliferation by regulating HIF1α expression.
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spelling doaj.art-8150466dc1f04f8698445a7e61ee511c2022-12-22T00:56:29ZengTabriz University of Medical SciencesAdvanced Pharmaceutical Bulletin2228-58812251-73082020-08-0110463063710.34172/apb.2020.076apb-28175MicroRNA-155-5p Diminishes in Vitro Ovarian Cancer Cell Viability by Targeting HIF1α ExpressionYsrafil Ysrafil0Indwiani Astuti1Sumadi Lukman Anwar2Ronny Martien3Firasti Agung Nugrahening Sumadi4Tirta Wardhana5Sofia Mubarika Haryana6Departement of Pharmacology and Therapy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Farmako Yogyakarta 55281, Indonesia.Departement of Pharmacology and Therapy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Farmako Yogyakarta 55281, Indonesia.Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Farmako Yogyakarta 55281, Indonesia.Departement of Pharmaceutics, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Sekip Utara Yogyakarta 55281, Indonesia.Faculty of Pharmacy Universitas Muhamadiah Malang, Jl. Bendungan Sutami No. 188-A 65145, Malang, Indonesia.Faculty of Medicine, Jenderal Soedirman University, Dr. Gumbreg, Mersi, Banyumas, Jawa Tengah 53112, Indonesia.Medicine and Health Sciences of Doctoral Program, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Farmako Yogyakarta 55281, Indonesia.Purpose: Ovarian cancer is the most lethal of gynecological malignancies. Recently, the development of microRNA (miRNA) -based therapeutics that could impact broad cellular programs, leading to inhibition of cancer cell viability, is gaining attention in the therapeutic landscape. The therapy is based on the presence of aberrant expressions of miRNA in cancer cells. Decreasing of tumor suppressor miRNA expression causes upregulation of oncoprotein, which worsens the prognosis of the ovarian cancer. Methods: miR-155-5p mimics were carried by chitosan nanoparticles using new nanotechnology methods. Cellular uptake of miRNA was assessed by fluorescence microscope while MTT and qPCR assay were used to determine miRNA profile and the effect of CS-NP/miRNA on SKOV3 cells. Results: Results of profiling validated using quantitative realtime-polymerase chain reaction (PCR) found one of the most altered tumor suppressor miRNAs, miR-155-5p was downregulated 892.15-fold. According to bioinformatic analysis we identified the miRNA could recognize and regulate HIF1α expression. Transfection of mimics for miR-155-5p showed significantly increased miR-155-5p endogen SKOV3 expression level compared to the control group. We found differences after transfection mimics for miR-155-5p 31.5 and 63 nanoMolar. Increasing of miR-155-5p endogen lead to diminished SKOV3 viability (by 30%; <0.05 at concentration 80 nanoMolar). These mimics may cause an increase in upregulated miR-155-5p endogen that can reduce HIF1α expression. Here we found 2-fold and 2.8-fold reduction of HIF1α expression level after transfection compared to the control group. Conclusion: According to these findings, the mimics miR-155-5p can inhibit ovarian cancer cell proliferation by regulating HIF1α expression.https://apb.tbzmed.ac.ir/PDF/apb-10-630.pdfmimics mir-155-5pskov3ovarian cancerhif1α
spellingShingle Ysrafil Ysrafil
Indwiani Astuti
Sumadi Lukman Anwar
Ronny Martien
Firasti Agung Nugrahening Sumadi
Tirta Wardhana
Sofia Mubarika Haryana
MicroRNA-155-5p Diminishes in Vitro Ovarian Cancer Cell Viability by Targeting HIF1α Expression
Advanced Pharmaceutical Bulletin
mimics mir-155-5p
skov3
ovarian cancer
hif1α
title MicroRNA-155-5p Diminishes in Vitro Ovarian Cancer Cell Viability by Targeting HIF1α Expression
title_full MicroRNA-155-5p Diminishes in Vitro Ovarian Cancer Cell Viability by Targeting HIF1α Expression
title_fullStr MicroRNA-155-5p Diminishes in Vitro Ovarian Cancer Cell Viability by Targeting HIF1α Expression
title_full_unstemmed MicroRNA-155-5p Diminishes in Vitro Ovarian Cancer Cell Viability by Targeting HIF1α Expression
title_short MicroRNA-155-5p Diminishes in Vitro Ovarian Cancer Cell Viability by Targeting HIF1α Expression
title_sort microrna 155 5p diminishes in vitro ovarian cancer cell viability by targeting hif1α expression
topic mimics mir-155-5p
skov3
ovarian cancer
hif1α
url https://apb.tbzmed.ac.ir/PDF/apb-10-630.pdf
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