Breast cancer (BC) is one of the leading causes of death in women worldwide. A major challenge in BC is chemoresistance, which is often modulated by epigenetic regulators such as long non-coding RNAs (lncRNAs). Because these regulator lncRNAs may play diverse roles, determining their specific pathways and/or functions is crucial to identify possible biomarkers and/or therapeutic targets for BC. In this study, we used gene expression microarrays in order to identify lncRNAs related to the BC biology. We found, among six differentially expressed (DE) lncRNAs, that the expression of lnc-ERP44-3:6 was consistently down-regulated in all breast tumor tissues compared to normal adjacent tissues of BC patients from northeastern Mexico. Since the role of lnc-ERP44-3:6 remains unknown in BC, we induced its transient overexpression in three different BC cell lines (i.e., MCF10A, MCF-7, and HCC1395) by transfection in order to elucidate its potential downstream effects. Remarkably, our results showed a significant increase in cell death and chemosensitivity to cisplatin at 48 h post-transfection (p < 0.01). In addition, we observed that GAPDH and FAS were up-regulated following the overexpression of lnc-ERP44-3:6. As GAPDH and FAS promote apoptosis in cancer, our findings suggest that the lnc-ERP44-3:6 overexpression induces cell death possibly via up-regulation of one or both genes in BC cell lines. To the best of our knowledge, this is the first study evaluating the overexpression of lnc-ERP44-3:6 and providing insights about its role in BC cells, which suggests that this lncRNA may be an interesting candidate as a potential therapeutic target for BC in our population. However, further studies would be needed to clarify the mechanisms by which an overexpression of lnc-ERP44-3:6 causes both cell death and chemosensitivity to cisplatin.
Bibliographical noteFunding Information:
Funding Statement: This research was funded by CONACYT (Grants INFRA-2013–204423 and S0008– 2014–1-233212 https://www.conacyt.gob.mx/) and PAICYT 2019 (Grant SA761-19 http://investigacion. uanl.mx/paicyt-provericyt/) for Carlos Córdova-Fletes.
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