Degradation of HOX Transcript Antisense RNA Provoked Apoptosis and Necrosis in Human Ovarian Cancer Cells

Abstract

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. 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. 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. 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.