Publication: Effects of knocking-down HIF-la on migration in human breast cancer cell MDA-MB-231.
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Date
2015
Authors
Rashid, Nur Sabrina Abd
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Abstract
Breast cancer is a global health concern worldwide. It is estimated that more than one million women are diagnosed with breast cancer every year and more than 410,000 will die from the diseases. The ability of breast cancer cell to metastases to a secondary tumor is the most dangerous aspect that leads to death. These characteristics of breast cancer cells are closely related to the condition called hypoxia which plays an important role in the progression of malignant disease. Solid tumor such as breast cancer has been associated with hypoxia. Under hypoxia, the stabilization of the key transcription factor hypoxia-inducible factor-la (HIF-la) can regulate the expression of many genes including those that involve in tumor metastasis process. Increase expression of voltage-gated sodium channels (VGSCs) particularly the cardiac isoform Nav 1.5 and its neonatal splice variant, nNav 1.5 have been implicated in the promotion of breast cancer aggressiveness. In aggressive breast cancer, there is positive correlation between HIF-la and Nav 1.5 as well as nNav 1.5. In order to study the interaction between the two molecules, this study is aimed at investigating the effects of knocking down HIF-la on the migration of breast cancer, MDA-MB-231 cells. The activity of HIF-la was silenced by targeting HIF-la using small interfering RNA (siRNA). The HIF-la, Nav 1.5 and nNav 1.5 mRNA level were measured using real-time PCRs and effects on cell migration were determined using transverse migration. The HIF-la siRNA reduced the level of Nav 1.5 and nNav 1.5 mRNA by •31 % and 12% respectively. Importantly, the siRNA supressed in vitro migration of MDA-MB-231 associated and that when this association was interrupted, tumor migration was also suppressed. xiv cells by ~37 %. From the siRNA result, it was concluded that HIF-la and VGSCs are