OSR1 downregulation indicates an unfavorable prognosis and activates the NF-κB pathway in ovarian cancer

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Abstract

Background

Odd-skipped related 1 (OSR1) has been reported as a tumor suppressor gene in various malignant tumors. The mechanism through which OSR1 regulates ovarian cancer (OC) progression remains unclear.

Materials and methods

Immunohistochemistry was utilized to evaluate OSR1 expression in patients with ovarian cancer. We investigated the association between clinicopathological parameters and OSR1 expression in OC patients and the influence of OSR1 expression on patient survival and prognosis. OC cells with OSR1 overexpression or knockdown were established and validated using Western blot and Quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The influence of OSR1 on the NF-κB pathway was examined by analyzing the p-IκBα, IκBα, p65, and p-p65 protein expression. In vitro assays, such as cell cycle assay, Cell Counting Kit-8 (CCK-8), transwell invasion assay, wound healing migration assay, enzyme-linked immunoassay (ELISA), and Annexin V/PI flow cytometry apoptosis assay, were conducted to explore the effect of OSR1 knockdown or dual inhibition of OSR1 and the NF-κB pathway on OC malignant biological behavior.

Results

OSR1 expression was downregulated in OC tissues, with significant associations observed between its expression and The International Federation of Gynecology and Obstetrics (FIGO) stage and tissue differentiation. Low OSR1 expression in OC patients correlated with reduced overall survival (OS) rates and poor prognosis . In vitro , experiments confirmed a negative correlation between OSR1 expression and NF-κB pathway activity. OSR1 knockdown facilitated OC cell malignant biological behavior, while the NF-κB pathway inhibitor (Bay 11-0782) reversed the impacts of OSR1 knockdown on cell proliferation, migration, invasion, and apoptosis.

Conclusion

Our findings indicate that OSR1 is downregulated and associated with OC prognosis. OSR1 suppresses NF-κB pathway activity and inhibits OC progression by targeting the NF-κB pathway.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12672-023-00778-0.

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Most cited references 43

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Cancer statistics, 2020

Rebecca Siegel, Kimberly D Miller, Ahmedin Jemal (2020)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2016) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2017) were collected by the National Center for Health Statistics. In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States. The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted. This progress is driven by long-term declines in death rates for the 4 leading cancers (lung, colorectal, breast, prostate); however, over the past decade (2008-2017), reductions slowed for female breast and colorectal cancers, and halted for prostate cancer. In contrast, declines accelerated for lung cancer, from 3% annually during 2008 through 2013 to 5% during 2013 through 2017 in men and from 2% to almost 4% in women, spurring the largest ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017. Yet lung cancer still caused more deaths in 2017 than breast, prostate, colorectal, and brain cancers combined. Recent mortality declines were also dramatic for melanoma of the skin in the wake of US Food and Drug Administration approval of new therapies for metastatic disease, escalating to 7% annually during 2013 through 2017 from 1% during 2006 through 2010 in men and women aged 50 to 64 years and from 2% to 3% in those aged 20 to 49 years; annual declines of 5% to 6% in individuals aged 65 years and older are particularly striking because rates in this age group were increasing prior to 2013. It is also notable that long-term rapid increases in liver cancer mortality have attenuated in women and stabilized in men. In summary, slowing momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers.

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Epithelial ovarian cancer: Evolution of management in the era of precision medicine

Stéphanie Lheureux, Marsela Braunstein, Amit Oza (2019)

Ovarian cancer is the second most common cause of gynecologic cancer death in women around the world. The outcomes are complicated, because the disease is often diagnosed late and composed of several subtypes with distinct biological and molecular properties (even within the same histological subtype), and there is inconsistency in availability of and access to treatment. Upfront treatment largely relies on debulking surgery to no residual disease and platinum-based chemotherapy, with the addition of antiangiogenic agents in patients who have suboptimally debulked and stage IV disease. Major improvement in maintenance therapy has been seen by incorporating inhibitors against poly (ADP-ribose) polymerase (PARP) molecules involved in the DNA damage-repair process, which have been approved in a recurrent setting and recently in a first-line setting among women with BRCA1/BRCA2 mutations. In recognizing the challenges facing the treatment of ovarian cancer, current investigations are enlaced with deep molecular and cellular profiling. To improve survival in this aggressive disease, access to appropriate evidence-based care is requisite. In concert, realizing individualized precision medicine will require prioritizing clinical trials of innovative treatments and refining predictive biomarkers that will enable selection of patients who would benefit from chemotherapy, targeted agents, or immunotherapy. Together, a coordinated and structured approach will accelerate significant clinical and academic advancements in ovarian cancer and meaningfully change the paradigm of care.

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Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2).

Claudia Allemani, Hannah K Weir, Helena Carreira … (2015)

Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control.

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Author and article information

Contributors

Ling Ouyang: ouyangling19640918@163.com

Journal

Journal ID (nlm-ta): Discov Oncol

Journal ID (iso-abbrev): Discov Oncol

Title: Discover. Oncology

Publisher: Springer US (New York )

ISSN (Electronic): 2730-6011

Publication date (Electronic): 29 August 2023

Publication date PMC-release: 29 August 2023

Publication date Collection: December 2023

Volume: 14

Electronic Location Identifier: 159

Affiliations

GRID grid.412467.2, ISNI 0000 0004 1806 3501, Department of Obstetrics and Gynecology, , Shengjing Hospital of China Medical University, ; No. 36, Sanhao Street, Heping District, Shenyang, 110004 Liaoning China

Article

Publisher ID: 778

DOI: 10.1007/s12672-023-00778-0

PMC ID: 10465422

PubMed ID: 37642735

SO-VID: 325f8fe7-be15-4430-b443-4e669c39eee6

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 13 May 2023

Date accepted : 22 August 2023

Custom metadata

Keywords: osr1,downregulation,unfavorable prognosis,nf-κb pathway,ovarian cancer

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Keywords: osr1, downregulation, unfavorable prognosis, nf-κb pathway, ovarian cancer

OSR1 downregulation indicates an unfavorable prognosis and activates the NF-κB pathway in ovarian cancer

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Abstract

Background

Materials and methods

Results

Conclusion

Supplementary Information

Related collections

Cancer Metabolism

Most cited references 43

Cancer statistics, 2020

Epithelial ovarian cancer: Evolution of management in the era of precision medicine

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2).

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Contributors

Journal

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