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Regulatory Mechanisms and Functional Roles of Hypoxia-Induced Long Non-Coding RNA MTORT1 in Breast Cancer Cells

Long non-coding RNAs (lncRNAs) have been found to participate in multiple genetic pathways in cancer. Also, mitochondria-associated lncRNAs have been discovered to modulate mitochondrial function and metabolism. Previously, we identified oxygen-responsive lncRNAs in MCF-7 breast cancer cells under d...

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Autores principales: Cheng, Yi-Chun, Su, Li-Yu, Chen, Li-Han, Lu, Tzu-Pin, Chuang, Eric Y., Tsai, Mong-Hsun, Chuang, Li-Ling, Lai, Liang-Chuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204045/
https://www.ncbi.nlm.nih.gov/pubmed/34141617
http://dx.doi.org/10.3389/fonc.2021.663114
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author Cheng, Yi-Chun
Su, Li-Yu
Chen, Li-Han
Lu, Tzu-Pin
Chuang, Eric Y.
Tsai, Mong-Hsun
Chuang, Li-Ling
Lai, Liang-Chuan
author_facet Cheng, Yi-Chun
Su, Li-Yu
Chen, Li-Han
Lu, Tzu-Pin
Chuang, Eric Y.
Tsai, Mong-Hsun
Chuang, Li-Ling
Lai, Liang-Chuan
author_sort Cheng, Yi-Chun
collection PubMed
description Long non-coding RNAs (lncRNAs) have been found to participate in multiple genetic pathways in cancer. Also, mitochondria-associated lncRNAs have been discovered to modulate mitochondrial function and metabolism. Previously, we identified oxygen-responsive lncRNAs in MCF-7 breast cancer cells under different oxygen concentrations. Among them, a novel mitochondria-encoded lncRNA, mitochondrial oxygen-responsive transcript 1 (MTORT1), was chosen for further investigation. Nuclear, cytoplasmic, and mitochondrial fractionation assays were performed to evaluate the endogenous expression levels of MTORT1 in breast cancer cells. In vitro proliferation and migration assays were conducted to investigate the functions of MTORT1 in breast cancer cells by knockdown of MTORT1. RNA immunoprecipitation and luciferase reporter assays were used to examine the physical binding between MTORT1 and microRNAs. Our results showed that MTORT1 had low endogenous expression levels in breast cancer cells and was mainly located in the mitochondria. Knockdown of MTORT1 enhanced cell proliferation and migration, implying a tumor suppressor role of this novel mitochondrial lncRNA. MTORT1 served as sponge of miR-26a-5p to up-regulate its target genes, CREB1 and STK4. Our findings shed some light on the characterization, function, and regulatory mechanism of the novel hypoxia-induced mitochondrial lncRNA MTORT1, which functions as a microRNA sponge and may inhibit breast cancer progression. These data suggest that MTORT1 may be a candidate for therapeutic targeting of breast cancer progression.
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spelling pubmed-82040452021-06-16 Regulatory Mechanisms and Functional Roles of Hypoxia-Induced Long Non-Coding RNA MTORT1 in Breast Cancer Cells Cheng, Yi-Chun Su, Li-Yu Chen, Li-Han Lu, Tzu-Pin Chuang, Eric Y. Tsai, Mong-Hsun Chuang, Li-Ling Lai, Liang-Chuan Front Oncol Oncology Long non-coding RNAs (lncRNAs) have been found to participate in multiple genetic pathways in cancer. Also, mitochondria-associated lncRNAs have been discovered to modulate mitochondrial function and metabolism. Previously, we identified oxygen-responsive lncRNAs in MCF-7 breast cancer cells under different oxygen concentrations. Among them, a novel mitochondria-encoded lncRNA, mitochondrial oxygen-responsive transcript 1 (MTORT1), was chosen for further investigation. Nuclear, cytoplasmic, and mitochondrial fractionation assays were performed to evaluate the endogenous expression levels of MTORT1 in breast cancer cells. In vitro proliferation and migration assays were conducted to investigate the functions of MTORT1 in breast cancer cells by knockdown of MTORT1. RNA immunoprecipitation and luciferase reporter assays were used to examine the physical binding between MTORT1 and microRNAs. Our results showed that MTORT1 had low endogenous expression levels in breast cancer cells and was mainly located in the mitochondria. Knockdown of MTORT1 enhanced cell proliferation and migration, implying a tumor suppressor role of this novel mitochondrial lncRNA. MTORT1 served as sponge of miR-26a-5p to up-regulate its target genes, CREB1 and STK4. Our findings shed some light on the characterization, function, and regulatory mechanism of the novel hypoxia-induced mitochondrial lncRNA MTORT1, which functions as a microRNA sponge and may inhibit breast cancer progression. These data suggest that MTORT1 may be a candidate for therapeutic targeting of breast cancer progression. Frontiers Media S.A. 2021-06-01 /pmc/articles/PMC8204045/ /pubmed/34141617 http://dx.doi.org/10.3389/fonc.2021.663114 Text en Copyright © 2021 Cheng, Su, Chen, Lu, Chuang, Tsai, Chuang and Lai https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Cheng, Yi-Chun
Su, Li-Yu
Chen, Li-Han
Lu, Tzu-Pin
Chuang, Eric Y.
Tsai, Mong-Hsun
Chuang, Li-Ling
Lai, Liang-Chuan
Regulatory Mechanisms and Functional Roles of Hypoxia-Induced Long Non-Coding RNA MTORT1 in Breast Cancer Cells
title Regulatory Mechanisms and Functional Roles of Hypoxia-Induced Long Non-Coding RNA MTORT1 in Breast Cancer Cells
title_full Regulatory Mechanisms and Functional Roles of Hypoxia-Induced Long Non-Coding RNA MTORT1 in Breast Cancer Cells
title_fullStr Regulatory Mechanisms and Functional Roles of Hypoxia-Induced Long Non-Coding RNA MTORT1 in Breast Cancer Cells
title_full_unstemmed Regulatory Mechanisms and Functional Roles of Hypoxia-Induced Long Non-Coding RNA MTORT1 in Breast Cancer Cells
title_short Regulatory Mechanisms and Functional Roles of Hypoxia-Induced Long Non-Coding RNA MTORT1 in Breast Cancer Cells
title_sort regulatory mechanisms and functional roles of hypoxia-induced long non-coding rna mtort1 in breast cancer cells
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204045/
https://www.ncbi.nlm.nih.gov/pubmed/34141617
http://dx.doi.org/10.3389/fonc.2021.663114
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