Hypoxia-Induced MALAT1 Promotes the Proliferation and Migration of Breast Cancer Cells by Sponging MiR-3064-5p
Hypoxia, a common process during tumor growth, can lead to tumor aggressiveness and is tightly associated with poor prognosis. Long noncoding RNAs (lncRNAs) are long ribonucleotides (>200 bases) with limited ability to translate proteins, and are known to affect many aspects of cellular funct...
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doaj-48c00ded520f4b4cb7a5726a77b651262021-05-03T09:22:06ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-05-011110.3389/fonc.2021.658151658151Hypoxia-Induced MALAT1 Promotes the Proliferation and Migration of Breast Cancer Cells by Sponging MiR-3064-5pChung-Hsien Shih0Li-Ling Chuang1Li-Ling Chuang2Mong-Hsun Tsai3Mong-Hsun Tsai4Li-Han Chen5Eric Y. Chuang6Eric Y. Chuang7Eric Y. Chuang8Tzu-Pin Lu9Tzu-Pin Lu10Liang-Chuan Lai11Liang-Chuan Lai12Graduate Institute of Physiology, College of Medicine, 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 Biotechnology, National Taiwan University, Taipei, TaiwanBioinformatics and Biostatistics Core, Center of Genomic and Precision Medicine, National Taiwan University, Taipei, TaiwanInstitute of Fisheries Science, College of Life Science, 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 Epidemiology and Preventive Medicine, National Taiwan University, Taipei, TaiwanGraduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, TaiwanBioinformatics and Biostatistics Core, Center of Genomic and Precision Medicine, National Taiwan University, Taipei, TaiwanHypoxia, a common process during tumor growth, can lead to tumor aggressiveness and is tightly associated with poor prognosis. Long noncoding RNAs (lncRNAs) are long ribonucleotides (>200 bases) with limited ability to translate proteins, and are known to affect many aspects of cellular function. One of their regulatory mechanisms is to function as a sponge for microRNA (miRNA) to modulate its biological functions. Previously, MALAT1 was identified as a hypoxia-induced lncRNA. However, the regulatory mechanism and functions of MALAT1 in breast cancer are still unclear. Therefore, we explored whether MALAT1 can regulate the functions of breast cancer cells through miRNAs. Our results showed the expression levels of MALAT1 were significantly up-regulated under hypoxia and regulated by HIF-1α and HIF-2α. Next, in contrast to previous reports, nuclear and cytoplasmic fractionation assays and fluorescence in situ hybridization indicated that MALAT1 was mainly located in the cytoplasm. Therefore, the labeling of MALAT1 as a nuclear marker should be done with the caveat. Furthermore, expression levels of miRNAs and RNA immunoprecipitation using antibody against AGO2 showed that MALAT1 functioned as a sponge of miRNA miR-3064-5p. Lastly, functional assays revealed that MALAT1 could promote cellular migration and proliferation of breast cancer cells. Our findings provide evidence that hypoxia-responsive long non-coding MALAT1 could be transcriptionally activated by HIF-1α and HIF-2α, act as a miRNA sponge of miR-3064-5p, and promote tumor growth and migration in breast cancer cells. These data suggest that MALAT1 may be a candidate for therapeutic targeting of breast cancer progression.https://www.frontiersin.org/articles/10.3389/fonc.2021.658151/fullhypoxialong non-coding RNAMALAT1breast cancerhypoxia inducible factor-1αmicroRNA |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chung-Hsien Shih Li-Ling Chuang Li-Ling Chuang Mong-Hsun Tsai Mong-Hsun Tsai Li-Han Chen Eric Y. Chuang Eric Y. Chuang Eric Y. Chuang Tzu-Pin Lu Tzu-Pin Lu Liang-Chuan Lai Liang-Chuan Lai |
spellingShingle |
Chung-Hsien Shih Li-Ling Chuang Li-Ling Chuang Mong-Hsun Tsai Mong-Hsun Tsai Li-Han Chen Eric Y. Chuang Eric Y. Chuang Eric Y. Chuang Tzu-Pin Lu Tzu-Pin Lu Liang-Chuan Lai Liang-Chuan Lai Hypoxia-Induced MALAT1 Promotes the Proliferation and Migration of Breast Cancer Cells by Sponging MiR-3064-5p Frontiers in Oncology hypoxia long non-coding RNA MALAT1 breast cancer hypoxia inducible factor-1α microRNA |
author_facet |
Chung-Hsien Shih Li-Ling Chuang Li-Ling Chuang Mong-Hsun Tsai Mong-Hsun Tsai Li-Han Chen Eric Y. Chuang Eric Y. Chuang Eric Y. Chuang Tzu-Pin Lu Tzu-Pin Lu Liang-Chuan Lai Liang-Chuan Lai |
author_sort |
Chung-Hsien Shih |
title |
Hypoxia-Induced MALAT1 Promotes the Proliferation and Migration of Breast Cancer Cells by Sponging MiR-3064-5p |
title_short |
Hypoxia-Induced MALAT1 Promotes the Proliferation and Migration of Breast Cancer Cells by Sponging MiR-3064-5p |
title_full |
Hypoxia-Induced MALAT1 Promotes the Proliferation and Migration of Breast Cancer Cells by Sponging MiR-3064-5p |
title_fullStr |
Hypoxia-Induced MALAT1 Promotes the Proliferation and Migration of Breast Cancer Cells by Sponging MiR-3064-5p |
title_full_unstemmed |
Hypoxia-Induced MALAT1 Promotes the Proliferation and Migration of Breast Cancer Cells by Sponging MiR-3064-5p |
title_sort |
hypoxia-induced malat1 promotes the proliferation and migration of breast cancer cells by sponging mir-3064-5p |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-05-01 |
description |
Hypoxia, a common process during tumor growth, can lead to tumor aggressiveness and is tightly associated with poor prognosis. Long noncoding RNAs (lncRNAs) are long ribonucleotides (>200 bases) with limited ability to translate proteins, and are known to affect many aspects of cellular function. One of their regulatory mechanisms is to function as a sponge for microRNA (miRNA) to modulate its biological functions. Previously, MALAT1 was identified as a hypoxia-induced lncRNA. However, the regulatory mechanism and functions of MALAT1 in breast cancer are still unclear. Therefore, we explored whether MALAT1 can regulate the functions of breast cancer cells through miRNAs. Our results showed the expression levels of MALAT1 were significantly up-regulated under hypoxia and regulated by HIF-1α and HIF-2α. Next, in contrast to previous reports, nuclear and cytoplasmic fractionation assays and fluorescence in situ hybridization indicated that MALAT1 was mainly located in the cytoplasm. Therefore, the labeling of MALAT1 as a nuclear marker should be done with the caveat. Furthermore, expression levels of miRNAs and RNA immunoprecipitation using antibody against AGO2 showed that MALAT1 functioned as a sponge of miRNA miR-3064-5p. Lastly, functional assays revealed that MALAT1 could promote cellular migration and proliferation of breast cancer cells. Our findings provide evidence that hypoxia-responsive long non-coding MALAT1 could be transcriptionally activated by HIF-1α and HIF-2α, act as a miRNA sponge of miR-3064-5p, and promote tumor growth and migration in breast cancer cells. These data suggest that MALAT1 may be a candidate for therapeutic targeting of breast cancer progression. |
topic |
hypoxia long non-coding RNA MALAT1 breast cancer hypoxia inducible factor-1α microRNA |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.658151/full |
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