Elsevier

Surgery

Volume 150, Issue 5, November 2011, Pages 916-922
Surgery

Original Communication
MicroRNA-10b is overexpressed in pancreatic cancer, promotes its invasiveness, and correlates with a poor prognosis

https://doi.org/10.1016/j.surg.2011.06.017Get rights and content

Background

MicroRNAs (miRNAs) have been gaining attention as new, key molecules that contribute to carcinogenesis. In pancreatic cancer, previous profiling analyses of miRNA expression have shown that several miRNAs are differently expressed in normal and cancerous tissues. Several pancreatic cancer-specific miRNAs differed, however, in each analysis.

Methods

We investigated the miRNA expression profiles of the pancreatic cancer cell lines CAPAN-1 and CFPAC1 and an immortalized human normal pancreatic ductal epithelial cell line (HPDE) using a high-throughput, TaqMan, qRT-PCR array analysis. We also analyzed the expression levels of this miRNA in microdissected (n = 15) and formalin-fixed, paraffin-embedded (FFPE) (n = 115) samples from pancreatic cancers by quantitative RT-PCR. Finally, we investigated the effects of this miRNA on the invasiveness of pancreatic cancer cells.

Results

Based on the microarray analysis, miR-372, miR-146a, miR-204, miR-10a, and miR-10b showed particularly large differences (>10-fold changes) between both pancreatic cell lines and HPDE cells. Thirteen of the 15 pancreatic cancer cell lines showed 2.1- to 36.4-fold (median, 15.3-fold) greater levels of miR-10b than HPDE cells. Microdissection analysis revealed that miR-10b exhibited greater expression levels in pancreatic cancer cells (n = 5) than in normal pancreatic ductal cells (n = 10) (P < .020). Analysis of FFPE samples showed that high miR-10b expression was associated with a lesser overall survival (P = .014). Furthermore, miR-10b correlated with the invasiveness of pancreatic cancer cells (P < .01).

Conclusion

miR-10b is overexpressed in pancreatic cancer and may be involved in the invasiveness in pancreatic cancer cells, thereby leading to a poor prognosis.

Section snippets

Cell culture and RNA isolation from cultured cells

Fifteen pancreatic cancer cell lines, namely ASPC-1, BxPC-3, KP-1N, KP-2, KP-3, PANC-1, and SUIT-2 (provided by H. Iguchi, MD, National Shikoku Cancer Center, Matsuyama, Japan), MIA-PaCa2 (Japanese Cancer Resource Bank, Tokyo, Japan), Capan-1, Capan-2, H48N, HS766T, CFPAC-1 and SW1990 (American Type Culture Collection, Manassas, VA), and NORP-1 (established in our laboratory) were used. A human pancreatic ductal epithelial cell line (HPDE6-E6E7 clone 6) immortalized by transduction with the E6

miRNA gene expression profiling of pancreatic cancer cell lines and HPDE cells using TaqMan® miRNA assays

When CFPAC-1 cells were compared with HPDE cells, 39 miRNAs showed significant differences in their expression levels (31 were upregulated and 8 were downregulated; Supplementary Table 1a); see online version. When CAPAN-1 cells were compared with HPDE cells, 30 miRNAs showed significant differences in their expression levels (12 were upregulated and 18 were downregulated; Supplementary Table 1b); see online version. Among these miRNAs, there were 15 miRNAs that showed significant differences

Discussion

In the present study, we identified several miRNAs, including miR-10b, that were differently expressed in pancreatic cancer cell lines compared with HPDE cells by miRNA profiling, and confirmed that miR-10b expression was observed frequently in pancreatic cancer cells using a panel of 15 pancreatic cancer lines. Furthermore, we showed that miR-10b was overexpressed in pancreatic cancer cells relative to normal pancreatic ductal cells. We also found that miR-10b expression promoted the

References (38)

  • Y. Hayashita et al.

    A polycistronic microRNA cluster, mir-17-92, is overexpressed in human lung cancers and enhances cell proliferation

    Cancer Res

    (2005)
  • R.C. Lee et al.

    An extensive class of small RNAs in Caenorhabditis elegans

    Science

    (2001)
  • N.C. Lau et al.

    An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans

    Science

    (2001)
  • M. Lagos-Quintana et al.

    Identification of novel genes coding for small expressed RNAs

    Science

    (2001)
  • O.A. Kent et al.

    A small piece in the cancer puzzle: MicroRNAs as tumor suppressors and oncogenes

    Oncogene

    (2006)
  • H.E. Gee et al.

    MicroRNA-10b and breast cancer metastasis

    Nature

    (2008)
  • S. Yekta et al.

    MicroRNA-directed cleavage of HOXB8 mRNA

    Science

    (2004)
  • L.P. Lim et al.

    Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs

    Nature

    (2005)
  • J. Takamizawa et al.

    Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival

    Cancer Res

    (2004)
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