Long non-coding RNA ROR confers arsenic trioxide resistance to HepG2 cells by inhibiting p53 expression.

Arsenic trioxide is an effective drug in the treatment of hematologic malignancies, but it has no obvious therapeutic effect on liver cancer. Long non-coding RNA ROR is a newly found long-noncoding RNA that has been reported to get involved in the regulation of chemo-resistance in multiple cancers. However, whether and how long non-coding RNA ROR gets involved in the resistance to arsenic trioxide in liver cancer has not been explored. In this study, We found that cellular apoptosis was increased by arsenic trioxide in liver cancer HepG2 cells; P53 expression was also increased by arsenic trioxide at both mRNA level and protein level, indicating that P53-dependent apoptosis is the main mechanism for arsenic trioxide to induce cytotoxicity in liver cancer HepG2 cells. Meanwhile, we found an obvious increase in the level of long non-coding RNA ROR in arsenic trioxide-treated HepG2 cells. By measuring the level of reactive oxygen species, glutathione, superoxide dismutase, and malondialdehyde, the product of lipid peroxidation, we further demonstrated that oxidative stress was a potential factor for both the activation of P53 expression and the increase in long non-coding RNA ROR expression. Through the knock-down of long non-coding RNA ROR by siRNA, we revealed that the activated long non-coding RNA ROR ameliorated arsenic trioxide-induced apoptosis by inhibiting P53 expression. Together, our study reported that long non-coding RNA ROR conferred arsenic trioxide resistance to liver cancer cells through inhibiting P53 expression, and long non-coding RNA ROR might be a novel sensitizing target for liver cancer treatment.