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. 2006 Oct;3(5):317-324.

Non-coding MicroRNAs hsa-let-7g and hsa-miR-181b are Associated with Chemoresponse to S-1 in Colon Cancer

Go Nakajima  1 , Kazuhiko Hayashi, Yaguang Xi, Kenji Kudo, Kazumi Uchida, Ken Takasaki, Masakazu Yamamoto, Jingfang Ju
Affiliations

Non-coding MicroRNAs hsa-let-7g and hsa-miR-181b are Associated with Chemoresponse to S-1 in Colon Cancer

Go Nakajima et al. Cancer Genomics Proteomics. 2006 Oct.

Abstract

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs (~22 nucleotides) that regulate gene expression at a post-transcriptional level via imperfect base pairing to the 3'-UTR of their target mRNAs. Previous studies from our group identified a number of deregulated miRNAs due to the loss of p53 tumor suppressor in colon cancer cell lines. To further investigate the in vivo biological significance of these miRNAs, the expressions of hsa-let-7g, hsa-miR-143, hsa-miR-145, hsa-miR-181b and hsa-miR-200c were investigated using formalin-fixed paraffin-embedded (FFPE) colon cancer specimens to evaluate the potential relationship with chemosensitivity and tumorigenesis. PATIENTS AND METHODS: Forty-six patients with recurrent or residual colon cancer lesions were treated with the 5-fluorouracil-based antimetabolite S-1. This includes twenty-one pairs of tumor and normal samples. Total RNAs were isolated and the expression level of each particular miRNA was quantified using real time qRT-PCR analysis. RESULTS: The expression levels of hsa-let-7g, hsa-miR-181b and hsa-miR-200c were over-expressed in tumor tissues compared to normal tissues. The expression levels of hsa-let-7g (p=0.03; Mann-Whitney test) and hsa-miR-181b (p=0.02; Mann-Whitney test) were strongly associated with clinical response to S-1. Although hsa-let-7g and hsa-miR-181b are strongly associated with patient's response to S-1 treatment, they are not significant prognostic factors for predicting survival. CONCLUSION: hsa-let-7g, hsa-miR-181b and hsa-miR-200c may be associated with tumorigenesis in colon cancer. In addition, hsa-let-7g and hsa-miR-181b may be potential indicators for chemoresponse to S-1 based chemotherapy.

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Figures

Figure 1
Figure 1
Hsa-miR-143 (A) and hsa-miR-145 (B) expressions in colorectal cancer and normal tissue specimens. Relative gene expression values were calculated using samples with the highest expression level of miRNA as 100% (see Materials and Methods). Hsa-miR-143 (p=0.1219; Wilcoxon test) (A) and hsa-miR-145 (p=0.0853; Wilcoxon test) (B).
Figure 2
Figure 2
Hsa-miR-200c expression in colorectal cancer and normal tissue specimens. Relative gene expression values were calculated using sample with the highest expression level of miRNA as 100% (see Materials and Methods). P=0.0001; Wilcoxon test.
Figure 3
Figure 3
Hsa-let-7g expression in colorectal cancer and normal tissue specimens. Relative gene expression values were calculated using sample with the highest expression level of miRNA as 100% (see Materials and Methods). P=0.0037; Wilcoxon test.
Figure 4
Figure 4
hsa-miR-181b expression in colorectal cancer and normal tissue specimens. Relative gene expression values were calculated using sample with the highest expression level of miRNA as 100% (Details see Materials and Methods). (p=0.0005; Wilcoxon test).
Figure 5
Figure 5
Response based on hsa-let-7g expression (p=0.0305; Mann-Whitney test). CR=complete response; PR=partial response; NC=no change; PD=progressive disease.
Figure 6
Figure 6
Kaplan-Meier overall survival curve based on hsa-let-7g expression (p=0.9166; Log-rank test).
Figure 7
Figure 7
Response based on hsa-miR-181b expression (p=0.0209; Mann-Whitney test). CR=complete response; PR=partial response; NC=no change; PD=progressive disease.
Figure 8
Figure 8
Kaplan-Meier overall survival curve based on hsa-miR-181b expression (p=0.1203; Log-rank test).
See this image and copyright information in PMC

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