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Published on: January 12, 2020
Long Intergenic Noncoding RNA OIN1 Promotes Ovarian Cancer Growth by Modulating Apoptosis-Related Gene Expression
Toshihiko Takeiwa1,2, Yuichi Mitobe1, Kazuhiro Ikeda1
1Division of Systems Medicine & Gene Therapy, Saitama Medical University, Hidaka, Saitama 350-1241, Japan.
Abstract:
Patients with advanced ovarian cancer usually exhibit high mortality rates, thus more efficient therapeutic strategies are expected to be developed. Recent transcriptomic studies revealed that long intergenic noncoding RNAs (lincRNAs) can be a new class of molecular targets for cancer management, because lincRNAs likely exert tissue-specific activities compared with protein-coding genes or other noncoding RNAs. We here show that an unannotated lincRNA originated from chromosome 10q21 and designated as ovarian cancer long intergenic noncoding RNA 1 (OIN1), is often overexpressed in ovarian cancer tissues compared with normal ovaries as analyzed by RNA sequencing. OIN1 silencing by specific siRNAs significantly exerted proliferation inhibition and enhanced apoptosis in ovarian cancer cells. Notably, RNA sequencing showed that OIN1 expression was negatively correlated with the expression of apoptosis-related genes ras association domain family member 5 (RASSF5) and adenosine A1 receptor (ADORA1), which were upregulated by OIN1 knockdown in ovarian cancer cells. OIN1-specifc siRNA injection was effective to suppress in vivo tumor growth of ovarian cancer cells inoculated in immunodeficient mice. Taken together, OIN1 could function as a tumor-promoting lincRNA in ovarian cancer through modulating apoptosis and will be a potential molecular target for ovarian cancer management.
Insights
A novel long intergenic noncoding RNA, OIN1, is overexpressed in ovarian cancer. Silencing OIN1 inhibits tumor growth and enhances apoptosis, identifying OIN1 as a potential therapeutic target for ovarian cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Advanced ovarian cancer has high mortality rates, necessitating novel therapeutic strategies.
- Long intergenic noncoding RNAs (lincRNAs) are emerging as potential molecular targets due to their tissue-specific activities.
Purpose of the Study:
- To investigate the role of a novel lincRNA, ovarian cancer long intergenic noncoding RNA 1 (OIN1), in ovarian cancer.
- To evaluate OIN1 as a potential therapeutic target for ovarian cancer management.
Main Methods:
- RNA sequencing was used to analyze OIN1 expression in ovarian cancer tissues and normal ovaries.
- OIN1 was silenced using small interfering RNAs (siRNAs) in ovarian cancer cells.
- Gene expression analysis was performed to assess the correlation between OIN1 and apoptosis-related genes (RASSF5, ADORA1).
- In vivo tumor growth was evaluated in immunodeficient mice following OIN1-specific siRNA injection.
Main Results:
- OIN1 was found to be overexpressed in ovarian cancer tissues compared to normal ovaries.
- OIN1 silencing significantly inhibited ovarian cancer cell proliferation and induced apoptosis.
- OIN1 expression was negatively correlated with apoptosis-related genes RASSF5 and ADORA1, which were upregulated upon OIN1 knockdown.
- OIN1-specific siRNA injection suppressed in vivo tumor growth in a mouse model.
Conclusions:
- OIN1 functions as a tumor-promoting lincRNA in ovarian cancer by modulating apoptosis.
- OIN1 represents a promising molecular target for the development of new ovarian cancer therapies.
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