Doxorubicin is a widely used anthracycline-based anti-tumor agent for both solid and liquid tumors. Mounting evidence has demonstrated that microRNAs (miRNAs) are involved in chemoresistance and tumorigenesis. However, the roles of microRNA-501-5p (miR-501) in doxorubicin resistance and gastric cancer cell proliferation and invasion are still not fully understood. In this study, we identified that BLID (BH3-like motif-containing protein, cell death inducer) was directly regulated by miR-501 at the post-transcriptional level in multiple gastric cancer cell lines. Endogenous miR-501 was higher, whereas BLID was lower, in doxorubicin-resistant gastric cancer SGC7901/ADR cells compared with their parental SGC7901 cells. miR-501 suppressed gastric cancer cell apoptosis, induced resistance to doxorubicin, and enhanced cell proliferation, migration, and invasion. Subcutaneous injection of miR-501 lentivirus-infected SGC7901 cells resulted in rapid growth of xenograft tumors and resistance to doxorubicin treatment, unlike injection of negative miRNA lentivirus-infected SGC7901 cells. This is achieved at least partially by directly targeting BLID and subsequent inactivation of caspase-9 and caspase-3 and phosphorylation of Akt. Taken together, miR-501 induces doxorubicin resistance and enhances the tumorigenesis of gastric cancer cells by suppressing BLID. miR-501 might be a potential target for doxorubicin resistance and gastric cancer therapy.

阿霉素是一种广泛用于实体和液体肿瘤的蒽环类抗肿瘤剂。越来越多的证据表明，微小 RNA (miRNA) 参与化学耐药性和肿瘤发生。然而，microRNA-501-5p (miR-501) 在多柔比星耐药和胃癌细胞增殖和侵袭中的作用仍未完全了解。在这项研究中，我们发现 BLID（含有 BH3 样基序的蛋白质，细胞死亡诱导剂）在多种胃癌细胞系的转录后水平上直接受 miR-501 调控。与其亲代 SGC7901 细胞相比，阿霉素耐药胃癌 SGC7901/ADR 细胞中的内源性 miR-501 更高，而 BLID 更低。miR-501 抑制胃癌细胞凋亡，诱导对多柔比星的耐药性，增强细胞增殖、迁移、和入侵。与注射阴性 miRNA 慢病毒感染的 SGC7901 细胞不同，皮下注射 miR-501 慢病毒感染的 SGC7901 细胞导致异种移植肿瘤的快速生长和对多柔比星治疗的抗性。这至少部分是通过直接靶向 BLID 并随后使 caspase-9 和 caspase-3 失活以及 Akt 磷酸化来实现的。总之，miR-501 诱导多柔比星耐药并通过抑制 BLID 增强胃癌细胞的肿瘤发生。miR-501 可能是阿霉素耐药和胃癌治疗的潜在靶点。这至少部分是通过直接靶向 BLID 并随后使 caspase-9 和 caspase-3 失活以及 Akt 磷酸化来实现的。总之，miR-501 诱导多柔比星耐药并通过抑制 BLID 增强胃癌细胞的肿瘤发生。miR-501 可能是阿霉素耐药和胃癌治疗的潜在靶点。这至少部分是通过直接靶向 BLID 并随后使 caspase-9 和 caspase-3 失活以及 Akt 磷酸化来实现的。总之，miR-501 诱导多柔比星耐药并通过抑制 BLID 增强胃癌细胞的肿瘤发生。miR-501 可能是阿霉素耐药和胃癌治疗的潜在靶点。