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Suppression of microRNA-629 enhances sensitivity of cervical cancer cells to 1′S-1′-acetoxychavicol acetate via regulating RSU1

Background: Cervical cancer is the fourth most frequent malignancy affecting women worldwide, but drug resistance and toxicities remain a major challenge in chemotherapy. The use of natural compounds is promising because they are less toxic and able to target multiple signaling pathways. The 1′S-1′-...

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Main Authors: Phuah, N.H., Azmi, M.N., Awang, Khalijah, Nagoor, Noor Hasima
Format: Article
Language:English
Published: Dove Medical Press 2017
Subjects:
Q Science (General)
QD Chemistry
QH Natural history
Online Access:http://eprints.um.edu.my/19062/1/Suppression_of_microRNA-629_enhances_sensitivity_of_cervical_cancer_cells_to_1%E2%80%B2S-1%E2%80%B2-acetoxychavicol_acetate_via_regulating_RSU1.pdf
http://eprints.um.edu.my/19062/
http://dx.doi.org/10.2147/OTT.S117492
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spelling my.um.eprints.190622019-03-01T09:10:41Z http://eprints.um.edu.my/19062/ Suppression of microRNA-629 enhances sensitivity of cervical cancer cells to 1′S-1′-acetoxychavicol acetate via regulating RSU1 Phuah, N.H. Azmi, M.N. Awang, Khalijah Nagoor, Noor Hasima Q Science (General) QD Chemistry QH Natural history Background: Cervical cancer is the fourth most frequent malignancy affecting women worldwide, but drug resistance and toxicities remain a major challenge in chemotherapy. The use of natural compounds is promising because they are less toxic and able to target multiple signaling pathways. The 1′S-1′-acetoxychavicol acetate (ACA), a natural compound isolated from wild ginger Alpinia conchigera, induced cytotoxicity on various cancer cells including cervical cancer. MicroRNAs (miRNAs) are short noncoding RNAs that regulate numerous biological processes, such as apoptosis and chemosensitivity. Past studies reported that miR-629 is upregulated in many cancers, and its expression was altered in ACA-treated cervical cancer cells. However, the role of miR-629 in regulating sensitivity toward ACA or other anticancer agents has not been reported. Hence, this study aims to investigate the role of miR-629 in regulating response toward ACA on cervical cancer cells. Methods: The miR-629 expression following transfection with miR-629 hairpin inhibitor and hairpin inhibitor negative control was measured using quantitative real-time polymerase chain reaction (RT-qPCR). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to investigate sensitivity toward ACA. Apoptosis was detected using Annexin V/propidium iodide and Caspase 3/7 assays. The gene target for miR-629 was identified using miRNA target prediction programs, luciferase reporter assay and Western blots. Gene overexpression studies were performed to evaluate its role in regulating response toward ACA. Results: Transfection with miR-629 hairpin inhibitor downregulated its expression in both cervical cancer cell lines. Suppression of miR-629 increased sensitivity toward ACA by reducing cell proliferation and inducing apoptosis. Luciferase reporter assay confirmed RSU1 as a direct target of miR-629. Overexpression of miR-629 decreased RSU1 protein expression, while inhibition of miR-629 increased RSU1 protein expression. Overexpression of RSU1 augmented antiproliferative and apoptosis-inducing effects of ACA. Conclusion: Our findings showed that combination of ACA with miR-629 and RSU1 may provide a potential strategy in treating cervical cancer. Dove Medical Press 2017 Article PeerReviewed application/pdf en http://eprints.um.edu.my/19062/1/Suppression_of_microRNA-629_enhances_sensitivity_of_cervical_cancer_cells_to_1%E2%80%B2S-1%E2%80%B2-acetoxychavicol_acetate_via_regulating_RSU1.pdf Phuah, N.H. and Azmi, M.N. and Awang, Khalijah and Nagoor, Noor Hasima (2017) Suppression of microRNA-629 enhances sensitivity of cervical cancer cells to 1′S-1′-acetoxychavicol acetate via regulating RSU1. OncoTargets and Therapy, 10. pp. 1695-1705. ISSN 1178-6930 http://dx.doi.org/10.2147/OTT.S117492 doi:10.2147/OTT.S117492
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
language English
topic Q Science (General)
QD Chemistry
QH Natural history
spellingShingle Q Science (General)
QD Chemistry
QH Natural history
Phuah, N.H.
Azmi, M.N.
Awang, Khalijah
Nagoor, Noor Hasima
Suppression of microRNA-629 enhances sensitivity of cervical cancer cells to 1′S-1′-acetoxychavicol acetate via regulating RSU1
description Background: Cervical cancer is the fourth most frequent malignancy affecting women worldwide, but drug resistance and toxicities remain a major challenge in chemotherapy. The use of natural compounds is promising because they are less toxic and able to target multiple signaling pathways. The 1′S-1′-acetoxychavicol acetate (ACA), a natural compound isolated from wild ginger Alpinia conchigera, induced cytotoxicity on various cancer cells including cervical cancer. MicroRNAs (miRNAs) are short noncoding RNAs that regulate numerous biological processes, such as apoptosis and chemosensitivity. Past studies reported that miR-629 is upregulated in many cancers, and its expression was altered in ACA-treated cervical cancer cells. However, the role of miR-629 in regulating sensitivity toward ACA or other anticancer agents has not been reported. Hence, this study aims to investigate the role of miR-629 in regulating response toward ACA on cervical cancer cells. Methods: The miR-629 expression following transfection with miR-629 hairpin inhibitor and hairpin inhibitor negative control was measured using quantitative real-time polymerase chain reaction (RT-qPCR). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to investigate sensitivity toward ACA. Apoptosis was detected using Annexin V/propidium iodide and Caspase 3/7 assays. The gene target for miR-629 was identified using miRNA target prediction programs, luciferase reporter assay and Western blots. Gene overexpression studies were performed to evaluate its role in regulating response toward ACA. Results: Transfection with miR-629 hairpin inhibitor downregulated its expression in both cervical cancer cell lines. Suppression of miR-629 increased sensitivity toward ACA by reducing cell proliferation and inducing apoptosis. Luciferase reporter assay confirmed RSU1 as a direct target of miR-629. Overexpression of miR-629 decreased RSU1 protein expression, while inhibition of miR-629 increased RSU1 protein expression. Overexpression of RSU1 augmented antiproliferative and apoptosis-inducing effects of ACA. Conclusion: Our findings showed that combination of ACA with miR-629 and RSU1 may provide a potential strategy in treating cervical cancer.
format Article
author Phuah, N.H.
Azmi, M.N.
Awang, Khalijah
Nagoor, Noor Hasima
author_facet Phuah, N.H.
Azmi, M.N.
Awang, Khalijah
Nagoor, Noor Hasima
author_sort Phuah, N.H.
title Suppression of microRNA-629 enhances sensitivity of cervical cancer cells to 1′S-1′-acetoxychavicol acetate via regulating RSU1
title_short Suppression of microRNA-629 enhances sensitivity of cervical cancer cells to 1′S-1′-acetoxychavicol acetate via regulating RSU1
title_full Suppression of microRNA-629 enhances sensitivity of cervical cancer cells to 1′S-1′-acetoxychavicol acetate via regulating RSU1
title_fullStr Suppression of microRNA-629 enhances sensitivity of cervical cancer cells to 1′S-1′-acetoxychavicol acetate via regulating RSU1
title_full_unstemmed Suppression of microRNA-629 enhances sensitivity of cervical cancer cells to 1′S-1′-acetoxychavicol acetate via regulating RSU1
title_sort suppression of microrna-629 enhances sensitivity of cervical cancer cells to 1′s-1′-acetoxychavicol acetate via regulating rsu1
publisher Dove Medical Press
publishDate 2017
url http://eprints.um.edu.my/19062/1/Suppression_of_microRNA-629_enhances_sensitivity_of_cervical_cancer_cells_to_1%E2%80%B2S-1%E2%80%B2-acetoxychavicol_acetate_via_regulating_RSU1.pdf
http://eprints.um.edu.my/19062/
http://dx.doi.org/10.2147/OTT.S117492
_version_ 1643690875992145920
score 13.211869

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