Long non-coding RNA placenta‑specific protein 2 regulates the chemosensitivity of cancer cells to cisplatin in hepatocellular carcinoma (HCC) by sponging microRNA-96 to upregulate X-linked inhibitor of apoptosis protein.
Long non-coding RNA placenta‑specific protein 2 regulates the chemosensitivity of cancer cells to cisplatin in hepatocellular carcinoma (HCC) by sponging microRNA-96 to upregulate X-linked inhibitor of apoptosis protein.
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DOI：
10.1080/21655979.2022.2056815
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发表时间：
2022-04
期刊：
影响因子：
4.9
通讯作者：
中科院分区：
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本研究旨在探讨lncRNA PLAC 2和XiaP在肝细胞癌（HCC）中的作用。HCC和配对的非肿瘤组织收集自62名接受基于顺铂的治疗的HCC患者。在基于顺铂的治疗后0、2和4个月，从所有患者收集血液样品（5 ml）并制备血浆样品。通过RT-qPCR测定组织和血浆样品中的LncRNA PLAC 2表达。通过过表达实验评估HCC细胞系中lncRNA PLAC 2和XiaP之间的相互作用。MTT法检测顺铂对细胞活力的影响，细胞凋亡检测顺铂对细胞凋亡的影响。通过进行RNA-RNA pulldown测定来分析lncRNA PLAC 2与可靶向XiaP的miR-96之间的直接相互作用。观察到lncRNA PLAC 2在HCC组织中比在非肿瘤组织中上调。肝癌组织中LncRNA PLAC 2的表达不受乙型肝炎病毒和丙型肝炎病毒的影响，但在基于顺铂的治疗后上调。类似地，顺铂处理HCC细胞增加了PLAC 2表达。LncRNA PLAC 2和XiaP过表达增加顺铂处理的HCC细胞的存活率并减少凋亡，而lncRNA PLAC 2敲低降低顺铂处理的HCC细胞的存活率并增加凋亡。Western blot分析显示，lncRNA PLAC 2增加肝癌细胞中XiaP蛋白的积累，而lncRNA PLAC 2 siRNA沉默降低肝癌细胞中XiaP的表达。LncRNA PLAC 2和miR-96直接相互作用，但它们不能调节彼此的表达。总之，lncRNA PLAC 2负调控HCC细胞对顺铂的化学敏感性，可能通过海绵状miR-96上调miR-96。
This study was conducted to investigate the roles of lncRNA PLAC2 and XiaP in hepatocellular carcinoma (HCC). HCC and paired non-tumor tissues were collected from 62 HCC patients who received cisplatin-based treatment. At 0, 2, and 4 months of post-cisplatin-based therapy, blood samples (5 ml) were collected from all patients and prepared plasma samples. LncRNA PLAC2 expression in tissue and plasma samples was determined by RT-qPCR. The interactions between lncRNA PLAC2 and XiaP in HCC cell lines were assessed by overexpression experiments. Cell viability and apoptosis under cisplatin treatment were analyzed by MTT assay and cell apoptosis assay, respectively. The direct interaction between lncRNA PLAC2 and miR-96, which can target XiaP, was analyzed by performing RNA–RNA pulldown assay. It was observed that lncRNA PLAC2 was upregulated in HCC tissues than in non-tumor tissues. LncRNA PLAC2 expression in HCC tissues was not affected by HBV and HCV but upregulated after cisplatin-based treatment. Similarly, cisplatin treatment of HCC cells increased PLAC2 expression. LncRNA PLAC2 and XiaP overexpression increased viability and decreased apoptosis of cisplatin-treated HCC cells, while lncRNA PLAC2 knockdown decreased viability and increased apoptosis of cisplatin-treated HCC cells. Western blot analysis showed that lncRNA PLAC2 increased XiaP protein accumulation, while lncRNA PLAC2 siRNA silencing decreased XiaP expression in HCC cells. LncRNA PLAC2 and miR-96 directly interacted with each other, while they failed to regulate the expression of each other. In conclusion, lncRNA PLAC2 negatively regulates the chemosensitivity of HCC cells to cisplatin, possibly by sponging miR-96 to upregulate miR-96.
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影响因子：
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10.1073/pnas.1420671112
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