Degradation of HOX Transcript Antisense RNA Provoked Apoptosis and Necrosis in Human Ovarian Cancer Cells
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ORIGINAL ARTICLE
Degradation of HOX Transcript Antisense RNA Provoked Apoptosis and Necrosis in Human Ovarian Cancer Cells Mahsa Sabet1 • Mohammadreza Sharifi2 • Mansour Heidari3 • Mohammad kazemi2 • Nahid Babaei1 Received: 8 February 2020 / Accepted: 28 March 2020 Ó Association of Gynecologic Oncologists of India 2020
Abstract Purpose Ovarian cancer (OC) is one of the common malignancies with poor survival rates in women. Long noncoding RNAs (lncRNAs) are a class of regulatory RNA via gene expression regulation and dysregulation results in several disorders such as cancer. LncRNA HOX transcript antisense RNA (HOTAIR) is reported to be upregulated in OC. It plays a major role in cell proliferation and metastasis. The aim of this study is to investigate the effect of HOTAIR blockage in OC cells proliferation and death. Methods We blocked HOTAIR in OC cell line SKOV3 by Antisense LNA GapmeRs. The qPCR and Annexin V/propidium iodide staining assay were performed at three time points after transfection. Moreover, we examined STAT3 and MAPK8 expression levels as cancer proliferation-associated agents under the influence of GapmeRs using qPCR at 24, 48 and 72 h after transfection. Results The rate of apoptotic cells increased in Antisense LNA GapmeRs-transfected group compared with the two other groups at all three time points. The ratio of the necrotic cell was also higher in Antisense LNA GapmeRs-treated group in contrary to the other groups in a time-dependent manner. However, among all selected genes only MAPK8 was significantly downregulated at 24 h, followed by upregulation at 48 and 72 h. STAT3 was remarkably increased in all three time points. Conclusion These data demonstrated that HOTAIR can act as an onco-lncRNA and its inhibition significantly boosted apoptosis and necrosis in the SKOV3 cell line. Our findings can pave the way for antisense-based therapy as a potentially effective approach in the treatment of OC. Keywords Apoptosis LncRNA HOTAIR Long noncoding RNA Necrosis Ovarian cancer
Introduction Ovarian cancer (OC) is the most common malignant gynecologic cancer and remains the leading cause of cancer-related death in the world. It accounts for 5% of female cancer deaths due mainly to low survival rates, largely & Mohammadreza Sharifi [email protected] 1
Department of Cell Biology and Genetics, Bushehr Branch, Islamic Azad University, Bushehr, Iran
2
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan 81744-176, Iran
3
Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran
driven by late-stage diagnoses [1]. The first line of OC treatment is surgery which is curative in more than 90% of patients. However, in most patients, the tumor has spread beyond the ovaries by the time it is diagnosed. Thus, combined treatment of surgery and chemotherapy appears to be more effective [2]. Despite advances in surgery and chemotherapy, the overall survival of epithelial ovarian cancer (EOC) patients remains
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