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Identification and validation of a novel long non-coding RNA (LINC01465) in ovarian cancer

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Abstract

Epithelial Ovarian Cancer (EOC) is a heterogeneous disease usually diagnosed at advanced stages. Therefore, early detection is crucial for better survival. Despite the advances in ovarian research, mechanisms underlying EOC carcinogenesis are not elucidated. We performed chromatin immunoprecipitation sequencing to identify genes regulated by E2F5, a transcription factor involved in ovarian carcinogenesis. Results revealed several putative candidate genes (115 protein-coding genes, 20 lncRNAs, 6 pseudogenes, and 4 miRNAs). A literature review and bioinformatics analysis of these genes revealed a novel lncRNA candidate (LINC01465) in EOC. We validated LINC01465 by quantifying its expression in EOC cell lines and selected OVSAHO and SKOV3 as a model with high LINC01465 levels. We silenced LINC01465 and performed proliferation, wound healing, invasion, and drug resistance assays. Knocking-down LINC01465 resulted in reduced migration, suggesting potential involvement in EOC. Furthermore, to identify the significance of LINC01465 in chemoresistance, we assessed the LINC01465 levels in A2780 S cells treated with malformin, which revealed higher LINC01465 expression as compared to untreated A2780S cells implying the involvement of LINC01465 in cell death. Thus, this study unraveled the repertoire of E2F5 regulated candidate genes and suggested a putative role of LINC01465 in malformin-induced cell death in EOC.

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Data availability statement

The data sets generated during and/or analyzed during this study are included in this published article.

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Funding

This research was funded by the grant from His Majesty Trust Fund (SR/MED/BIOC/14/01).

Author information

Author notes

  1. Shika Hanif Malgundkar and Nada Abdullah Hassan have contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, PC 123, PO Box 35, Muscat, Sultanate of Oman

    Shika Hanif Malgundkar, Nada Abdullah Hassan, Hala Al Badi, Zainab Al Hashami, Hamida Al Barwani & Yahya Tamimi

  2. College of Medicine, Qatar University, PO Box 2713, Doha, Qatar

    Ishita Gupta

  3. Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, PC 123, PO Box 35, Muscat, Sultanate of Oman

    Ikram A. Burney

  4. Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, PC 123, PO Box 35, Muscat, Sultanate of Oman

    Hamad Al Riyami

  5. Obstetrics and Gynecology, College of Medicine and Health Sciences, Sultan Qaboos University, PC 123, PO Box 35, Muscat, Sultanate of Oman

    Moza Al Kalbani

  6. Department of Pathology, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE

    Ritu Lakhtakia

  7. Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo, Japan

    Aikou Okamoto

Authors
  1. Shika Hanif Malgundkar
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Contributions

YT participated in the conceptualization and designed the project methodology. SH, NA, HB, IG, ZH, and HB performed the experiments. SH interpreted the data and wrote the manuscript under the supervision of YT. AO, IB, MK, HB, and RL contributed to discussing and reviewing the clinical part of the project.

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Correspondence to Yahya Tamimi.

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Malgundkar, S.H., Hassan, N.A., Al Badi, H. et al. Identification and validation of a novel long non-coding RNA (LINC01465) in ovarian cancer. Human Cell 36, 762–774 (2023). https://doi.org/10.1007/s13577-022-00842-x

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