ABCC6P1 pseudogene induces ABCC6 upregulation and multidrug resistance in breast cancer

The elevated drug efflux by ABC transports has been considered the primary mechanism of drug resistance in cancer. Recently, non-coding RNAs, such as pseudogenes, have been proposed to be involved in transporter-mediated drug resistance in cancer. The human genome has 22 ABC transporter pseudogenes. Among these pseudogenes, ABCC6P1 has co-expression with its ancestral gene in various human tissues. In the present study, we assessed the effect of ABCC6P1 pseudogene overexpression on ABCC6 expression and drug resistance.

The ABCC6P1 was transfected into the MCF-7 and MDA-MB-231 cells. In ABCC6P1-overexpressing cells, the ABCC6 level significantly increased. The results of cell treatment with doxorubicin, 5-fluorouracil, cisplatin, and paclitaxel showed that the survival of ABCC6P1-overexpressing cells was higher than normal cells. Furthermore, uptake of doxorubicin was lower in ABCC6P1-overexpressing cells.

In conclusion, our results show that overexpression of ABCC6P1 pseudogene induces the drug resistance phenotype, possibly through activation of the ancestral gene.