Functional characterization of miR-708 microRNA in telomerase positive and negative human cancer cells

Abstract Activation of a telomere length maintenance mechanism (TMM), including telomerase and alternative lengthening of telomeres (ALT), is essential for replicative immortality of tumor cells, although its regulatory mechanisms are incompletely understood. We conducted a microRNA (miRNA) microarr...

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Autores principales:	Zeenia Kaul, Caroline T. Y. Cheung, Priyanshu Bhargava, Anissa Notifa Sari, Yue Yu, He Huifu, Hemant Bid, Jeremy D. Henson, Joanna Groden, Roger R. Reddel, Sunil C. Kaul, Renu Wadhwa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/600b71e497384ddca0eed83a1f48466d
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spelling	oai:doaj.org-article:600b71e497384ddca0eed83a1f48466d2021-12-02T15:09:07ZFunctional characterization of miR-708 microRNA in telomerase positive and negative human cancer cells10.1038/s41598-021-96096-y2045-2322https://doaj.org/article/600b71e497384ddca0eed83a1f48466d2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96096-yhttps://doaj.org/toc/2045-2322Abstract Activation of a telomere length maintenance mechanism (TMM), including telomerase and alternative lengthening of telomeres (ALT), is essential for replicative immortality of tumor cells, although its regulatory mechanisms are incompletely understood. We conducted a microRNA (miRNA) microarray analysis on isogenic telomerase positive (TEP) and ALT cancer cell lines. Amongst nine miRNAs that showed difference in their expression in TEP and ALT cancer cells in array analysis, miR-708 was selected for further analysis since it was consistently highly expressed in a large panel of ALT cells. miR-708 in TEP and ALT cancer cells was not correlated with C-circle levels, an established feature of ALT cells. Its overexpression induced suppression of cell migration, invasion, and angiogenesis in both TEP and ALT cells, although cell proliferation was inhibited only in TEP cells suggesting that ALT cells may have acquired the ability to escape inhibition of cell proliferation by sustained miR-708 overexpression. Further, cell proliferation regulation in TEP cells by miR708 appears to be through the CARF-p53 pathway. We demonstrate here that miR-708 (i) is the first miRNA shown to be differentially regulated in TEP and ALT cancer cells, (ii) possesses tumor suppressor function, and (iii) deregulates CARF and p21WAF1-mediated signaling to limit proliferation in TEP cells.Zeenia KaulCaroline T. Y. CheungPriyanshu BhargavaAnissa Notifa SariYue YuHe HuifuHemant BidJeremy D. HensonJoanna GrodenRoger R. ReddelSunil C. KaulRenu WadhwaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zeenia Kaul Caroline T. Y. Cheung Priyanshu Bhargava Anissa Notifa Sari Yue Yu He Huifu Hemant Bid Jeremy D. Henson Joanna Groden Roger R. Reddel Sunil C. Kaul Renu Wadhwa Functional characterization of miR-708 microRNA in telomerase positive and negative human cancer cells
description	Abstract Activation of a telomere length maintenance mechanism (TMM), including telomerase and alternative lengthening of telomeres (ALT), is essential for replicative immortality of tumor cells, although its regulatory mechanisms are incompletely understood. We conducted a microRNA (miRNA) microarray analysis on isogenic telomerase positive (TEP) and ALT cancer cell lines. Amongst nine miRNAs that showed difference in their expression in TEP and ALT cancer cells in array analysis, miR-708 was selected for further analysis since it was consistently highly expressed in a large panel of ALT cells. miR-708 in TEP and ALT cancer cells was not correlated with C-circle levels, an established feature of ALT cells. Its overexpression induced suppression of cell migration, invasion, and angiogenesis in both TEP and ALT cells, although cell proliferation was inhibited only in TEP cells suggesting that ALT cells may have acquired the ability to escape inhibition of cell proliferation by sustained miR-708 overexpression. Further, cell proliferation regulation in TEP cells by miR708 appears to be through the CARF-p53 pathway. We demonstrate here that miR-708 (i) is the first miRNA shown to be differentially regulated in TEP and ALT cancer cells, (ii) possesses tumor suppressor function, and (iii) deregulates CARF and p21WAF1-mediated signaling to limit proliferation in TEP cells.
format	article
author	Zeenia Kaul Caroline T. Y. Cheung Priyanshu Bhargava Anissa Notifa Sari Yue Yu He Huifu Hemant Bid Jeremy D. Henson Joanna Groden Roger R. Reddel Sunil C. Kaul Renu Wadhwa
author_facet	Zeenia Kaul Caroline T. Y. Cheung Priyanshu Bhargava Anissa Notifa Sari Yue Yu He Huifu Hemant Bid Jeremy D. Henson Joanna Groden Roger R. Reddel Sunil C. Kaul Renu Wadhwa
author_sort	Zeenia Kaul
title	Functional characterization of miR-708 microRNA in telomerase positive and negative human cancer cells
title_short	Functional characterization of miR-708 microRNA in telomerase positive and negative human cancer cells
title_full	Functional characterization of miR-708 microRNA in telomerase positive and negative human cancer cells
title_fullStr	Functional characterization of miR-708 microRNA in telomerase positive and negative human cancer cells
title_full_unstemmed	Functional characterization of miR-708 microRNA in telomerase positive and negative human cancer cells
title_sort	functional characterization of mir-708 microrna in telomerase positive and negative human cancer cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/600b71e497384ddca0eed83a1f48466d
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Functional characterization of miR-708 microRNA in telomerase positive and negative human cancer cells

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