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MicroRNA-21 induces resistance to the anti-tumour effect of interferon-α/5-fluorouracil in hepatocellular carcinoma cells.

Tomimaru Y, Eguchi H, Nagano H, Wada H, Tomokuni A, Kobayashi S, Marubashi S, Takeda Y, Tanemura M, Umeshita K, Doki Y, Mori M - Br. J. Cancer (2010)

Bottom Line: The aim of this study was to investigate the anti-tumour effects of microRNA (miR)-21 on the sensitivity of HCC cells to IFN-α/5-FU and whether miR-21 can be used as a predictor of the response to such therapy in HCC.Annexin V assay showed that the percentage of apoptotic cells was significantly lower in cells transfected with pre-miR-21 than control cells.The miR-21 in HCC cell lines and clinical HCC samples is a significant modulator of the anti-tumour effect of IFN-α and 5-FU.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, Suita, 2-2 Yamadaoka E-2, Osaka 565-0871, Japan.

ABSTRACT

Background: We reported recently the clinical efficiency of interferon (IFN)-α/5-fluorouracil (5-FU) combination therapy in advanced hepatocellular carcinoma (HCC). However, prediction of the response to the combination therapy remains unsatisfactory. The aim of this study was to investigate the anti-tumour effects of microRNA (miR)-21 on the sensitivity of HCC cells to IFN-α/5-FU and whether miR-21 can be used as a predictor of the response to such therapy in HCC.

Methods: Changes in the sensitivity of HCC cells (PLC/PRF/5 and HepG2) to IFN-α/5-FU were examined after transfection with pre-miR-21 or anti-miR-21. The correlation between miR-21 expression level, evaluated by qRT-PCR, and response to the therapy was also investigated in clinical HCC specimens.

Results: Hepatocellular carcinoma cells transfected with pre-miR-21 were significantly resistant to IFN-α/5-FU. Annexin V assay showed that the percentage of apoptotic cells was significantly lower in cells transfected with pre-miR-21 than control cells. Transfection of anti-miR-21 rendered HCC cells sensitive to IFN-α/5-FU, and such sensitivity was weakened by transfection of siRNAs of target molecules, PETN and PDCD4. miR-21 expression in clinical HCC specimens was significantly associated with the clinical response to the IFN-α/5-FU combination therapy and survival rate.

Conclusions: The miR-21 in HCC cell lines and clinical HCC samples is a significant modulator of the anti-tumour effect of IFN-α and 5-FU. This suggests that miR-21 is a potentially suitable marker for the prediction of the clinical response to the IFN-α/5-FU combination therapy.

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Related in: MedlinePlus

The expression level of miR-21 in five HCC cell lines including PLC/PRF/5, HuH7, HLE, HLF, and HepG2, and clinical samples from 30 patients with advanced HCC. The miR-21 expression was normalised by the average expression in non-tumoural tissues. The expression in tumoural tissue was significantly higher than in non-tumoural tissue (*P<0.05). Data are mean±s.d. T =tumoural tissue; N= non-tumoural tissue.
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fig1: The expression level of miR-21 in five HCC cell lines including PLC/PRF/5, HuH7, HLE, HLF, and HepG2, and clinical samples from 30 patients with advanced HCC. The miR-21 expression was normalised by the average expression in non-tumoural tissues. The expression in tumoural tissue was significantly higher than in non-tumoural tissue (*P<0.05). Data are mean±s.d. T =tumoural tissue; N= non-tumoural tissue.

Mentions: The expression of miR-21 was examined in tumoural tissue and non-tumoural tissue of the 30 patients with advanced HCC and also in the HCC cell lines. The expression in tumoural tissue was significantly higher compared with non-tumoural tissue, as reported previously by Meng et al (2007) (P<0.0001) (Figure 1). The expression in the HCC cell lines varied as shown in Figure 1.


MicroRNA-21 induces resistance to the anti-tumour effect of interferon-α/5-fluorouracil in hepatocellular carcinoma cells.

Tomimaru Y, Eguchi H, Nagano H, Wada H, Tomokuni A, Kobayashi S, Marubashi S, Takeda Y, Tanemura M, Umeshita K, Doki Y, Mori M - Br. J. Cancer (2010)

The expression level of miR-21 in five HCC cell lines including PLC/PRF/5, HuH7, HLE, HLF, and HepG2, and clinical samples from 30 patients with advanced HCC. The miR-21 expression was normalised by the average expression in non-tumoural tissues. The expression in tumoural tissue was significantly higher than in non-tumoural tissue (*P<0.05). Data are mean±s.d. T =tumoural tissue; N= non-tumoural tissue.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2990590&req=5

fig1: The expression level of miR-21 in five HCC cell lines including PLC/PRF/5, HuH7, HLE, HLF, and HepG2, and clinical samples from 30 patients with advanced HCC. The miR-21 expression was normalised by the average expression in non-tumoural tissues. The expression in tumoural tissue was significantly higher than in non-tumoural tissue (*P<0.05). Data are mean±s.d. T =tumoural tissue; N= non-tumoural tissue.
Mentions: The expression of miR-21 was examined in tumoural tissue and non-tumoural tissue of the 30 patients with advanced HCC and also in the HCC cell lines. The expression in tumoural tissue was significantly higher compared with non-tumoural tissue, as reported previously by Meng et al (2007) (P<0.0001) (Figure 1). The expression in the HCC cell lines varied as shown in Figure 1.

Bottom Line: The aim of this study was to investigate the anti-tumour effects of microRNA (miR)-21 on the sensitivity of HCC cells to IFN-α/5-FU and whether miR-21 can be used as a predictor of the response to such therapy in HCC.Annexin V assay showed that the percentage of apoptotic cells was significantly lower in cells transfected with pre-miR-21 than control cells.The miR-21 in HCC cell lines and clinical HCC samples is a significant modulator of the anti-tumour effect of IFN-α and 5-FU.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, Suita, 2-2 Yamadaoka E-2, Osaka 565-0871, Japan.

ABSTRACT

Background: We reported recently the clinical efficiency of interferon (IFN)-α/5-fluorouracil (5-FU) combination therapy in advanced hepatocellular carcinoma (HCC). However, prediction of the response to the combination therapy remains unsatisfactory. The aim of this study was to investigate the anti-tumour effects of microRNA (miR)-21 on the sensitivity of HCC cells to IFN-α/5-FU and whether miR-21 can be used as a predictor of the response to such therapy in HCC.

Methods: Changes in the sensitivity of HCC cells (PLC/PRF/5 and HepG2) to IFN-α/5-FU were examined after transfection with pre-miR-21 or anti-miR-21. The correlation between miR-21 expression level, evaluated by qRT-PCR, and response to the therapy was also investigated in clinical HCC specimens.

Results: Hepatocellular carcinoma cells transfected with pre-miR-21 were significantly resistant to IFN-α/5-FU. Annexin V assay showed that the percentage of apoptotic cells was significantly lower in cells transfected with pre-miR-21 than control cells. Transfection of anti-miR-21 rendered HCC cells sensitive to IFN-α/5-FU, and such sensitivity was weakened by transfection of siRNAs of target molecules, PETN and PDCD4. miR-21 expression in clinical HCC specimens was significantly associated with the clinical response to the IFN-α/5-FU combination therapy and survival rate.

Conclusions: The miR-21 in HCC cell lines and clinical HCC samples is a significant modulator of the anti-tumour effect of IFN-α and 5-FU. This suggests that miR-21 is a potentially suitable marker for the prediction of the clinical response to the IFN-α/5-FU combination therapy.

Show MeSH
Related in: MedlinePlus