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miR-30 family promotes migratory and invasive abilities in CD133+ pancreatic cancer stem-like cells

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Abstract

Pancreatic cancer is a deadly disease with a poor prognosis. Recently, miRNAs have been reported to be abnormally expressed in several cancers and play a role in cancer development and progression. However, the role of miRNA in cancer stem cells remains unclear. Therefore, our aim was to investigate the role of miRNA in the CD133+ pancreatic cancer cell line Capan-1M9 because CD133 is a putative marker of pancreatic cancer stem cells. Using miRNA microarray, we found that the expression level of the miR-30 family decreased in CD133 genetic knockdown shCD133 Capan-1M9 cells. We focused on miR-30a, -30b, and -30c in the miR-30 family and created pancreatic cancer cell sublines, each transfected with these miRNAs. High expression of miR-30a, -30b, or -30c had no effect on cell proliferation and sphere forming. In contrast, these sublines were resistant to gemcitabine, which is a standard anticancer drug for pancreatic cancer, and in addition, promoted migration and invasion. Moreover, mesenchymal markers were up-regulated by these miRNAs, suggesting that mesenchymal phenotype is associated with an increase in migration and invasion. Thus, our study demonstrated that high expression of the miR-30 family modulated by CD133 promotes migratory and invasive abilities in CD133+ pancreatic cancer cells. These findings suggest that targeted therapies to the miR-30 family contribute to the development of novel therapies for CD133+ pancreatic cancer stem cells.

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Acknowledgments

We thank Mr. Toru Obara and Ms. Shoko Ueno for their assistance with the pathological analysis, Ms. Ryoko Imakiire for her gene profiling analysis, and Miss Hiromi Tokushige and Ms. Yoshiko Setogawa for their clerical assistance. We wish to thank the Joint Research Laboratory, Kagoshima University Graduate School of Medical and Dental Sciences, for the use of their facilities. This work was supported by JSPS KAKENHI [Grant-in-Aid for Scientific Research (B)] Grant Number 25293288 (to S.T.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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Authors and Affiliations

  1. Division of Cancer and Regenerative Medicine, Frontier Biomedical Science and Swine Research Center, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan

    Koichiro Tsukasa, Qiang Ding, Yumi Miyazaki, Shyuichiro Matsubara & Sonshin Takao

  2. Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Canada

    Qiang Ding

  3. Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan

    Shoji Natsugoe

  4. Tanegashima Medical Center, 7463 Nishino-omote, Kagoshima, 891-3198, Japan

    Sonshin Takao

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  1. Koichiro Tsukasa
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  2. Qiang Ding
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  3. Yumi Miyazaki
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  4. Shyuichiro Matsubara
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  5. Shoji Natsugoe
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Correspondence to Sonshin Takao.

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Tsukasa, K., Ding, Q., Miyazaki, Y. et al. miR-30 family promotes migratory and invasive abilities in CD133+ pancreatic cancer stem-like cells. Human Cell 29, 130–137 (2016). https://doi.org/10.1007/s13577-016-0137-7

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  • DOI: https://doi.org/10.1007/s13577-016-0137-7

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