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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doaj-51e3102f83aa45fe9950307f51826f722021-06-01T04:52:31ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-06-011110.3389/fonc.2021.663114663114Regulatory Mechanisms and Functional Roles of Hypoxia-Induced Long Non-Coding RNA MTORT1 in Breast Cancer CellsYi-Chun Cheng0Li-Yu Su1Li-Han Chen2Tzu-Pin Lu3Tzu-Pin Lu4Eric Y. Chuang5Eric Y. Chuang6Eric Y. Chuang7Mong-Hsun Tsai8Mong-Hsun Tsai9Li-Ling Chuang10Li-Ling Chuang11Liang-Chuan Lai12Liang-Chuan Lai13Institute of Physiology, College of Medicine, National Taiwan University, Taipei, TaiwanInstitute of Physiology, College of Medicine, National Taiwan University, Taipei, TaiwanInstitute of Fisheries Science, College of Life Science, National Taiwan University, Taipei, TaiwanInstitute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, TaiwanBioinformatics and Biostatistics Core, Center of Genomic and Precision Medicine, National Taiwan University, Taipei, TaiwanBioinformatics and Biostatistics Core, Center of Genomic and Precision Medicine, National Taiwan University, Taipei, TaiwanGraduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, TaiwanCollage of Biomedical Engineering, China Medical University, Taichung, TaiwanBioinformatics and Biostatistics Core, Center of Genomic and Precision Medicine, National Taiwan University, Taipei, TaiwanInstitute of Biotechnology, National Taiwan University, Taipei, TaiwanSchool of Physical Therapy and Graduate Institute of Rehabilitation Science, College of Medicine, Chang Gung University, Taoyuan, TaiwanDepartment of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Taoyuan, TaiwanInstitute of Physiology, College of Medicine, National Taiwan University, Taipei, TaiwanBioinformatics and Biostatistics Core, Center of Genomic and Precision Medicine, National Taiwan University, Taipei, TaiwanLong 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.https://www.frontiersin.org/articles/10.3389/fonc.2021.663114/fulllong noncoding RNAmitochondriahypoxiafunctionmicroRNAbreast cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yi-Chun Cheng Li-Yu Su Li-Han Chen Tzu-Pin Lu Tzu-Pin Lu Eric Y. Chuang Eric Y. Chuang Eric Y. Chuang Mong-Hsun Tsai Mong-Hsun Tsai Li-Ling Chuang Li-Ling Chuang Liang-Chuan Lai Liang-Chuan Lai |
spellingShingle |
Yi-Chun Cheng Li-Yu Su Li-Han Chen Tzu-Pin Lu Tzu-Pin Lu Eric Y. Chuang Eric Y. Chuang Eric Y. Chuang Mong-Hsun Tsai Mong-Hsun Tsai Li-Ling Chuang Li-Ling Chuang Liang-Chuan Lai Liang-Chuan Lai Regulatory Mechanisms and Functional Roles of Hypoxia-Induced Long Non-Coding RNA MTORT1 in Breast Cancer Cells Frontiers in Oncology long noncoding RNA mitochondria hypoxia function microRNA breast cancer |
author_facet |
Yi-Chun Cheng Li-Yu Su Li-Han Chen Tzu-Pin Lu Tzu-Pin Lu Eric Y. Chuang Eric Y. Chuang Eric Y. Chuang Mong-Hsun Tsai Mong-Hsun Tsai Li-Ling Chuang Li-Ling Chuang Liang-Chuan Lai Liang-Chuan Lai |
author_sort |
Yi-Chun Cheng |
title |
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_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_sort |
regulatory mechanisms and functional roles of hypoxia-induced long non-coding rna mtort1 in breast cancer cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-06-01 |
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. |
topic |
long noncoding RNA mitochondria hypoxia function microRNA breast cancer |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.663114/full |
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