Molecular pathways and functional analysis of miRNA expression associated with paclitaxel-induced apoptosis in hepatocellular carcinoma cells.
BACKGROUND
We postulated that microRNAs (miRNAs) might be involved in hepatocellular carcinoma (HCC) targeted chemotherapy with paclitaxel. This study sought to generate a list of potential miRNA-based biomarkers and their potential targets to better understand the response to paclitaxel treatment in HCC.


METHODS
Cell viability proliferation assays were conducted to test the sensitivity of the HepG2 cells to paclitaxel. The morphological changes of apoptosis were assessed with 4',6-diamidino-2-phenylindole staining. Differential expression patterns of miRNA in the HepG2 cells either treated or not treated were analyzed using miRNA microarrays.


RESULTS
The array experiments have identified 54 miRNAs whose basal expression levels differed by >2-fold and p < 0.05 between the two phenotypic groups. The data were validated by a quantitative real-time PCR of 8 selected miRNAs (miR-21, miR-1274a, miR-1260, miR-1290, miR-508-5p, miR-877, miR-1246, miR-183*). The PI3K/Akt, mitogen-activated protein kinase (MAPK), TGF-β, ErbB, p53, cell cycle, mammalian target of rapamycin, and Jak-STAT signaling pathways were involved in paclitaxel-induced apoptosis.


CONCLUSIONS
The manipulation of one or more of these miRNAs could be an important approach for the improved management of paclitaxel therapy.
National Engineering Research Center for Miniaturized Detection System, College of Life Sciences, Northwest University, Xi'an, China.
H
H
Yan
S
S
Wang
H
H
Yu
J
J
Zhu
C
C
Chen
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D017239:Paclitaxel / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D035683:MicroRNAs; D017239:Paclitaxel