Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
Cancer Med. 2019 Apr;8(4):1604-1618. doi: 10.1002/cam4.1860. Epub 2019 Mar 6.
The current investigation explored the synthetic contribution of lncRNA H19, miR-130a-3p, and miR-17-5p to radio-resistance and chemo-sensitivity of cardiac cancer cells. Totally 284 human cardiac cancer tissues were gathered, and they have been pathologically diagnosed. The cardiac cancer cells were isolated with utilization of the mechanic method. Moreover, cisplatin, adriamycin, mitomycin, and 5-fluorouracil were designated as the chemotherapies, and single-dose X-rays were managed as the radiotherapy for cardiac cancer cells. We also performed luciferase reporter gene assay to verify the targeted relationship between H19 and miR-130a-3p, as well as between H19 and miR-17-5p. Finally, mice models were established to examine the functions of H19, miR-130a-3p, and miR-17-5p on the development of cardiac cancer. The study results indicated that H19, miR-130a-3p, and miR-17-5p expressions within cardiac cancer tissues were significantly beyond those within adjacent nontumor tissues (P < 0.05), and H19 expression was positively correlated with both miR-130a-3p (r = 0.43) and miR-17-5p (r = 0.49) expressions. The half maximal inhibitory concentrations (IC50) of cisplatin, adriamycin, mitomycin, and 5-fluorouracil for cardiac cancer cells were, respectively, determined as 2.01 μg/mL, 8.35 μg/mL, 24.44 μg/mL, and 166.42 μg/mL. The overexpressed H19, miR-130a-3p, and miR-17-5p appeared to improve the survival rate and viability of cardiac cancer cells that were exposed to chemotherapies and X-rays (all P < 0.05). It was also drawn from luciferase reporter gene assay that H19 could directly target miR-130a-3p and miR-17-5p, thereby modifying the sensitivity of cardiac cancer cells to drugs and X-rays (P < 0.05). Finally, the mice models also produced larger tumor size and higher tumor weight, when H19, miR-130a-3p, or miR-17-5p expressions were up-regulated within them (P < 0.05). In conclusion, H19 could act on miR-130a-3p or miR-17-5p to alter the radio- and chemo-sensitivities of cardiac cancer cells, helping to improve the radio-/chemotherapies for cardiac cancer.
本研究旨在探讨长链非编码 RNA H19、miR-130a-3p 和 miR-17-5p 对心脏癌细胞放射抵抗和化疗敏感性的综合作用。共收集 284 例人心脏癌组织,经病理诊断。利用机械方法分离心脏癌细胞。此外,顺铂、阿霉素、丝裂霉素和 5-氟尿嘧啶被指定为化疗药物,单次剂量 X 射线被用作心脏癌细胞的放射治疗。我们还进行了荧光素酶报告基因检测,以验证 H19 与 miR-130a-3p 以及 H19 与 miR-17-5p 之间的靶向关系。最后,建立了小鼠模型,以研究 H19、miR-130a-3p 和 miR-17-5p 对心脏癌发展的作用。研究结果表明,心脏癌组织中 H19、miR-130a-3p 和 miR-17-5p 的表达明显高于相邻非肿瘤组织(P<0.05),且 H19 表达与 miR-130a-3p(r=0.43)和 miR-17-5p(r=0.49)表达呈正相关。心脏癌细胞对顺铂、阿霉素、丝裂霉素和 5-氟尿嘧啶的半数最大抑制浓度(IC50)分别为 2.01μg/ml、8.35μg/ml、24.44μg/ml 和 166.42μg/ml。过表达 H19、miR-130a-3p 和 miR-17-5p 可提高心脏癌细胞对化疗和 X 射线的存活率和活力(均 P<0.05)。荧光素酶报告基因检测还表明,H19 可直接靶向 miR-130a-3p 和 miR-17-5p,从而改变心脏癌细胞对药物和 X 射线的敏感性(P<0.05)。最后,当 H19、miR-130a-3p 或 miR-17-5p 在其中上调时,小鼠模型也产生了更大的肿瘤大小和更高的肿瘤重量(P<0.05)。总之,H19 可以作用于 miR-130a-3p 或 miR-17-5p 来改变心脏癌细胞的放射和化疗敏感性,有助于改善心脏癌的放射/化学治疗。