Department of Human Genetics, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
Mol Biol Rep. 2022 Oct;49(10):9633-9639. doi: 10.1007/s11033-022-07872-6. Epub 2022 Aug 28.
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.
ABC 转运蛋白的药物外排增加被认为是癌症药物耐药的主要机制。最近，非编码 RNA（如假基因）被认为参与了癌症中介导转运蛋白的药物耐药性。人类基因组中有 22 个 ABC 转运蛋白假基因。在这些假基因中，ABCC6P1 在各种人体组织中与其祖先基因共同表达。在本研究中，我们评估了 ABCC6P1 假基因过表达对 ABCC6 表达和耐药性的影响。
将 ABCC6P1 转染到 MCF-7 和 MDA-MB-231 细胞中。在 ABCC6P1 过表达细胞中，ABCC6 水平显著增加。用阿霉素、5-氟尿嘧啶、顺铂和紫杉醇处理细胞的结果表明，ABCC6P1 过表达细胞的存活率高于正常细胞。此外，ABCC6P1 过表达细胞对阿霉素的摄取较低。
总之，我们的结果表明，ABCC6P1 假基因的过表达诱导了耐药表型，可能通过激活祖先基因。
