Long noncoding RNA H19 promotes chemotherapy resistance in choriocarcinoma cells

Abstract

Choriocarcinoma (CC) is a trophoblast tumor prone to early distant organ metastases. At present, the main treatment for CC is chemotherapy, but chemotherapy resistance readily occurs and leads to treatment failure. H19 is a long noncoding RNA, and its abnormal expression has been found in various tumors, including CC. H19 is also considered to be related to the drug resistance mechanism of the same cancers. To investigate the role of H19 in drug‐resistant CC cells, the following experiments were designed. We used human CC cell line JEG‐3 to establish cell lines resistant to methotrexate and 5‐fluorouracil (JEG‐3/MTX and JEG‐3/5‐FU) and detected the expression of H19 in JEG‐3, JEG‐3/MTX, JEG‐3/5‐FU cells, JEG‐3 with MTX, and JEG‐3 with 5‐FU. We found that the expression of H19 in the JEG‐3/MTX and JEG‐3/5‐FU cells were significantly higher than that in JEG‐3 cells. JEG‐3 cells were treated with MTX or 5‐FU for and quantitative real‐time polymerase chain reaction assay revealed that H19 messenger RNA expression increased. Furthermore, after H19 was knocked out, the drug resistance index of the JEG‐3/MTX and JEG‐3/5‐FU cells decreased; the proliferation, migration, and invasion ability diminished significantly; and apoptosis increased significantly. Finally, we detected the total and phosphorylation protein expression of phosphatidylinositol‐3‐kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) in the JEG‐3/MTX and JEG‐3/5‐FU cells. The total protein of PI3K, AKT, and mTOR in the H19 knockout resistant cells showed no significant change relative to those in the H19 non‐knockout resistant cells, whereas the phosphorylated proteins of PI3K, AKT, and mTOR were significantly decreased. Phosphorylated proteins of PI3K, AKT, and mTOR in the JEG‐3/MTX and JEG‐3/5‐FU cells were significantly higher than that in JEG‐3 cells. After using inhibition of phosphorylated PI3K/AKT/mTOR, the proliferation, migration, and invasion ability of the JEG‐3/MTX and JEG‐3/5‐FU cells diminished significantly; and apoptosis increased significantly. On the basis of the above experiments, we concluded that H19 is related to the drug resistance of CC, and the knockout of H19 can reduce the drug resistance of resistant CC cells; and decrease the proliferative, migratory, and invasive ability; and increase the apoptosis. PI3K/AKT/mTOR pathway might be involved in H19‐mediated effects. H19 is expected to be a therapeutic target for the treatment of drug‐resistant chorionic carcinoma.

LncRNA HORAS5 Promotes Taxane Resistance in Castration-Resistant Prostate Cancer via a BCL2A1-Dependent Mechanism

“…Our data show that HORAS5 overexpression increases cabazitaxel resistance via regulation of apoptotic signals. This is consistent with previous studies implicating lncRNAs as regulators of cell apoptosis [63,64] and as mediators of drug resistance [65,66]. In AR + PCa cell, HORAS5 acts mainly by stabilising the AR mRNA, thereby activating AR-target genes, such as the oncogenic KIAA0101 [22].…”

An Overview of the Role of Long Non-Coding RNAs in Human Choriocarcinoma

“…In CC, there is an abnormal expression of H19 where it plays an important role in tumor development [ 62 ]. Yu et al investigated the role of H19 in CC cells which are resistant to drugs and demonstrated that H19 , through the regulation of the PI3K/AKT/mTOR pathway, results in drug resistance together with increased proliferative, migratory, and invasive ability of CC cells [ 61 ]. This suggests H19 may be a potential therapeutic target for the treatment of drug-resistant CC.…”

Integrated Bioinformatic Analysis of Competing Endogenous RNA Network of Choriocarcinoma

“…Choriocarcinoma (CC) is an aggressive, malignant trophoblastic neoplasm, either gestational or nongestational in origin [ 1 ]. Although CC is sensitive to chemotherapy, about 20% of patients with drug-resistant CC experience treatment failure and are at increased risk of metastatic lesions, hysterectomy, and decreased fertility [ 2 , 3 ]. Early metastasis and drug resistance in chemotherapy remain a clinical challenge in CC.…”