LncRNA MALAT1 Regulates the Progression and Cisplatin Resistance of Ovarian Cancer Cells via Modulating miR-1271-5p/E2F5 Axis

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Abstract

Background

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) were reported to be related to the development of ovarian cancer (OC). In this study, the functional mechanisms of lncRNA metastasis associated with lung adenocarcinoma transcript 1 (MALAT1) and microRNA-1271-5p (miR-1271-5p) were explored in OC.

Methods

The level of MALAT1, miR-1271-5p, or E2F transcription factor 5 (E2F5) was detected by qRT-PCR. MTT assay, flow cytometry analysis and transwell migration and invasion assays were performed to determine cell proliferation, apoptosis, migration and invasion, respectively. E2F5 protein expression was detected by Western blot. The interaction between miR-1271-5p and MALAT1 or E2F transcription factor 5 (E2F5) was confirmed by the dual-luciferase reporter assay.

Results

MALAT1 and E2F5 level were increased, while miR-1271-5p level was decreased in cisplatin (DDP)-resistant OC tissues and cells. MALAT1 knockdown or miR-1271-5p upregulation decreased IC ₅₀ of cisplatin, and inhibited cell proliferation, migration, invasion, and facilitated cell apoptosis in DDP-resistant OC cells. Moreover, MALAT1 sponged miR-1271-5p to upregulate E2F5 expression. Besides, MALAT1 knockdown decreased DDP resistance, inhibited cell proliferation, migration, invasion, and promoted cell apoptosis by sponging miR-1271-5p to downregulate E2F5 expression in DDP-resistant OC cell.

Conclusion

We demonstrated that MALAT1 mediated DDP-resistant OC development through miR-1271-5p/E2F5 axis, providing the theoretical basis for OC therapy.

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Most cited references 38

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MicroRNAs: genomics, biogenesis, mechanism, and function.

David P Bartel (2004)

MicroRNAs (miRNAs) are endogenous approximately 22 nt RNAs that can play important regulatory roles in animals and plants by targeting mRNAs for cleavage or translational repression. Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.

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Ovarian cancer statistics, 2018

Lindsey A Torre, Britton Trabert, Carol DeSantis … (2018)

In 2018, there will be approximately 22,240 new cases of ovarian cancer diagnosed and 14,070 ovarian cancer deaths in the United States. Herein, the American Cancer Society provides an overview of ovarian cancer occurrence based on incidence data from nationwide population-based cancer registries and mortality data from the National Center for Health Statistics. The status of early detection strategies is also reviewed. In the United States, the overall ovarian cancer incidence rate declined from 1985 (16.6 per 100,000) to 2014 (11.8 per 100,000) by 29% and the mortality rate declined between 1976 (10.0 per 100,000) and 2015 (6.7 per 100,000) by 33%. Ovarian cancer encompasses a heterogenous group of malignancies that vary in etiology, molecular biology, and numerous other characteristics. Ninety percent of ovarian cancers are epithelial, the most common being serous carcinoma, for which incidence is highest in non-Hispanic whites (NHWs) (5.2 per 100,000) and lowest in non-Hispanic blacks (NHBs) and Asians/Pacific Islanders (APIs) (3.4 per 100,000). Notably, however, APIs have the highest incidence of endometrioid and clear cell carcinomas, which occur at younger ages and help explain comparable epithelial cancer incidence for APIs and NHWs younger than 55 years. Most serous carcinomas are diagnosed at stage III (51%) or IV (29%), for which the 5-year cause-specific survival for patients diagnosed during 2007 through 2013 was 42% and 26%, respectively. For all stages of epithelial cancer combined, 5-year survival is highest in APIs (57%) and lowest in NHBs (35%), who have the lowest survival for almost every stage of diagnosis across cancer subtypes. Moreover, survival has plateaued in NHBs for decades despite increasing in NHWs, from 40% for cases diagnosed during 1992 through 1994 to 47% during 2007 through 2013. Progress in reducing ovarian cancer incidence and mortality can be accelerated by reducing racial disparities and furthering knowledge of etiology and tumorigenesis to facilitate strategies for prevention and early detection. CA Cancer J Clin 2018;68:284-296. © 2018 American Cancer Society.

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Long non-coding RNAs: insights into functions.

Tim Mercer, Marcel E Dinger, John S. Mattick (2009)

In mammals and other eukaryotes most of the genome is transcribed in a developmentally regulated manner to produce large numbers of long non-coding RNAs (ncRNAs). Here we review the rapidly advancing field of long ncRNAs, describing their conservation, their organization in the genome and their roles in gene regulation. We also consider the medical implications, and the emerging recognition that any transcript, regardless of coding potential, can have an intrinsic function as an RNA.

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Author and article information

Journal

Journal ID (nlm-ta): Cancer Manag Res

Journal ID (iso-abbrev): Cancer Manag Res

Journal ID (publisher-id): cmar

Journal ID (pmc): cancmanres

Title: Cancer Management and Research

Publisher: Dove

ISSN (Electronic): 1179-1322

Publication date (Electronic): 12 October 2020

Publication date Collection: 2020

Volume: 12

Pages: 9999-10010

Affiliations

[1 ]Department of Gynecology, The First People’s Hospital of Lianyungang , Lianyungang 222000, Peoples’ Republic of China

Author notes

Correspondence: Yuqin WangDepartment of Gynecology, The First People’s Hospital of Lianyungang , No. 6, Zhenhua Road, Lianyungang, Jiangsu222000, Peoples’ Republic of ChinaTel +86-0518-85605008 Email Chenan34032875@163.com

Article

Publisher ID: 261979

DOI: 10.2147/CMAR.S261979

PMC ID: 7567574

PubMed ID: 33116856

SO-VID: 709132eb-bd5f-48d4-b2f4-07939f91cc34

License:

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

History

Date received : 28 May 2020

Date accepted : 03 September 2020

Page count

Figures: 7, Tables: 1, References: 38, Pages: 12

Funding

Funded by: no funding;

There is no funding to report.

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LncRNA MALAT1 Regulates the Progression and Cisplatin Resistance of Ovarian Cancer Cells via Modulating miR-1271-5p/E2F5 Axis

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Abstract

Background

Methods

Results

Conclusion

Related collections

Karger: Oncology

Most cited references 38

MicroRNAs: genomics, biogenesis, mechanism, and function.

Ovarian cancer statistics, 2018

Long non-coding RNAs: insights into functions.

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