Abstract 5887: A microRNA signature panel predicts differential sensitivity of liver cancer cells to chemotherapeutic drugs

• Published in: Cancer research (Chicago, Ill.) Ill.), 2018-07, Vol.78 (13_Supplement), p.5887-5887
• Main Authors: Tryndyak, Volodymyr, Kindrat, Iryna, McDannell, Brigit, Beland, Frederick A., Pogribny, Igor P.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2018-5887

Hepatocellular carcinoma (HCC) is one of the deadliest human cancers, with a steadily rising incidence in the United States and worldwide. Most HCC patients are diagnosed at intermediate and advanced stages of the disease when treatment options are limited to systematic therapy; however, the individual patient response to treatment varies significantly. In the present study, we investigated an ability of the base-line mircoRNA (miRNA) expression profile in human liver cancer cells to predict the response to chemotherapeutic drugs currently used in the clinical management of HCC. Next-generation sequencing analysis of the base-line miRNA expression in naïve SK-Hep-1, Hep3B, HepG2, Huh7, and PLC/PRF/5 cells showed different miRNA expression profiles, among which 70 miRNAs were in common among all cell lines. A detailed analysis of the common miRNAs revealed that SK-Hep-1 and HepG2 cells exhibited the major differences in their base-line miRNA expression. The cancer cells were then treated with sorafenib, doxorubicin hydrochloride, 5-fluorouracil, and cisplatin, and cell survival was determined by cell viability assays. The sensitivity of liver cancer cells to these chemotherapeutic drugs varied among the cell lines, with SK-Hep-1 cells being the most resistant to sorafenib and the most sensitive to 5-fluorouracil. In contrast, HepG2 cells were the most sensitive to sorafenib, doxorubicin hydrochloride, and cisplatin treatment and the most resistant to 5-fluorouracil. Further analysis of miRNA expression in these two cell lines identified 107 distinct differentially expressed miRNAs (cut-off > 5-fold) involved in the regulation of critical cancer-related pathways. Among these differentially expressed miRNAs, the basal expression pattern of several miRNAs corresponded to the miRNA expression patterns associated with an acquired cancer-cell-resistant phenotype to sorafenib. Specifically, miR-10a and miR-181 were up-regulated and miR-27b, miR-34a, miR-122, miR-200a, and miR-200b were down-regulated in naïve SK-Hep-1 cells. Likewise, the low basal expression of miR-30a, miR-30b, miR-27a, miR-125b, miR-135b, miR-149, and miR-218 and over-expression of miR-143 and miR-200a in naïve HepG2 were similar to that in cells with an acquired 5-fluorouracil cancer-resistant phenotype. These findings were confirmed in functional transfection experiments that showed ectopic modulation of miRNA levels in SK-Hep-1 and HepG2 modified their drug sensitivity to sorafenib and 5-flu