LncRNA H19 interacted with miR-130a-3p and miR-17-5p to modify radio-resistance and chemo-sensitivity of cardiac carcinoma cells.Cancer Med 2019; 8(4):1604-1618CM
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 (rs = 0.43) and miR-17-5p (rs = 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.