Up-regulation of microRNAs, miR21 and miR23a in human liver cancer cells treated with Coptidis rhizoma aqueous extract

Abstract

Abstract. Coptidis rhizoma (cr; huanglian in chinese) has been used for the treatment of cancer in chinese medicine, and recent studies have supported its use in cancer therapy. micrornas (mirnas) play an important role in the pathophysiology of human cancers. We examined alterations in the miRNA profile of hepatocellular carcinoma (HCC) cells after treatment with Coptidis rhizoma aqueous extract (craE). an on-chip microarray method was used to detect alterations in the expression profile of miRNAs in human hcc mhcc97-l cells after exposure to 175 µg/ml craE. altered expression of several mirnas was detected in the mhcc97-l cells after treatment with 175 µg/ml craE. the microarray results were validated by quantitative real-time pcr (qrt-pcr). consistent results were obtained; qrt-pcr confirmed that both miR-21 and miR-23a were significantly up-regulated. targetScan and pictar microrna databases were used to predict the possible target genes of the altered mirnas. the results showed that the altered mirnas after craE treatment may serve as markers for the therapy of liver cancer. To the best of our knowledge, this is the first report on the up-regulation of mirnas, mir21 and mir23a in human liver cancer cells treated with craE. Our results suggest that craE targets mir-21 and mir-23a in liver cancer cells supporting the potential application of craE in the treatment of hcc.Introduction hepatocellular carcinoma (hcc) is associated with a dismal patient outcome, and its incidence rate continues to rise (1).at present, only 10-20% of patients with hcc are eligible for surgical therapy (2). the results of therapeutic treatment for liver cancer remain unsatisfactory. micrornas (mirnas) are single-stranded rna molecules, approximately 21-23 nucleotides in length, which are able to regulate gene expression at either the transcriptional or post-transcriptional level. mirnas are encoded by genes that are transcribed from dna, but are not translated into protein.This type of non-coding RNA was first described in 1993 by lee et al (3), which was later referred to as microrna (4). Subsequent studies in recent years have demonstrated a significant difference in miRNA expression profiles in human malignancies, including chronic lymphocytic leukaemia, pediatric Burkitt's lymphoma, gastric cancer, lung cancer and large-cell lymphoma. These findings suggest that miRNAs may play an important role in carcinogenesis as a novel class of oncogenes or tumor-suppressor genes (5,6). thus, mirnas have been considered as novel targets for cancer therapy.Coptidis rhizoma (cr) has been used in chinese medicine for thousands of years. previous studies have demonstrated that cr exhibits a variety of pharmacological actions, including anti-neoplastic, anti-oxidative, anti-bacterial, anti-viral, antiinflammatory, anti-hyperglycemic, anti-hypertensive and liver protective effects (7-9). the anti-tumor action of cr has been extensively reported. cr induces multiple signal transduction pathways to promote cancer cell apoptosis, inhibiting tumor ce...

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