Role of anti-oncomirs miR-143 and-145 in human colorectal tumors

Y. Akao, Yoshihito Nakagawa, I. Hirata, A. Iio, T. Itoh, K. Kojima, R. Nakashima, Y. Kitade, T. Naoe

Research output: Contribution to journalArticle

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Abstract

We examined the expression levels of microRNAs (miRNAs (miRs)) in colorectal tumors (63 cancer specimens and 65 adenoma specimens) and paired non-tumorous tissues. Decreased expression of miR-143 and-145 was frequently observed in the adenomas and cancers tested, compared with miR-34a downregulation and miR-21 upregulation. Expression profiles of miR-143 and-145 were not associated with any clinical features. As the downregulation of miR-143 and-145 was observed even in the early phase of adenoma formation, the decreased expression of both miRs would appear to contribute mainly to the initiation step of tumorigenesis, not to the progression stage, and not to clinical prognostic factors. For clinical application, we changed the sequences of the passenger strand in the miR-143 duplex and performed chemical modification at the 3′-overhang portion of miR-143, leading to greater activity and stability to nuclease. The cell growth inhibitory effect of the chemically modified synthetic miR-143 in vitro was greater than that of endogenous miR-143. The miR-143 showed a significant tumor-suppressive effect on xenografted tumors of DLD-1 human colorectal cancer cells. These findings suggest that miR-143 and-145 are important onco-related genes for the initiation step of colorectal tumor development and that the chemically modified synthetic miR-143 may be a hopeful candidate as an RNA medicine for the treatment of colorectal tumors.

Original languageEnglish
Pages (from-to)398-408
Number of pages11
JournalCancer Gene Therapy
Volume17
Issue number6
DOIs
Publication statusPublished - 01-06-2010

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Colorectal Neoplasms
MicroRNAs
Adenoma
Neoplasms
Down-Regulation
Carcinogenesis
Up-Regulation
RNA
Growth
Genes

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Molecular Medicine
  • Molecular Biology

Cite this

Akao, Y., Nakagawa, Y., Hirata, I., Iio, A., Itoh, T., Kojima, K., ... Naoe, T. (2010). Role of anti-oncomirs miR-143 and-145 in human colorectal tumors. Cancer Gene Therapy, 17(6), 398-408. https://doi.org/10.1038/cgt.2009.88
Akao, Y. ; Nakagawa, Yoshihito ; Hirata, I. ; Iio, A. ; Itoh, T. ; Kojima, K. ; Nakashima, R. ; Kitade, Y. ; Naoe, T. / Role of anti-oncomirs miR-143 and-145 in human colorectal tumors. In: Cancer Gene Therapy. 2010 ; Vol. 17, No. 6. pp. 398-408.
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Akao, Y, Nakagawa, Y, Hirata, I, Iio, A, Itoh, T, Kojima, K, Nakashima, R, Kitade, Y & Naoe, T 2010, 'Role of anti-oncomirs miR-143 and-145 in human colorectal tumors', Cancer Gene Therapy, vol. 17, no. 6, pp. 398-408. https://doi.org/10.1038/cgt.2009.88

Role of anti-oncomirs miR-143 and-145 in human colorectal tumors. / Akao, Y.; Nakagawa, Yoshihito; Hirata, I.; Iio, A.; Itoh, T.; Kojima, K.; Nakashima, R.; Kitade, Y.; Naoe, T.

In: Cancer Gene Therapy, Vol. 17, No. 6, 01.06.2010, p. 398-408.

Research output: Contribution to journalArticle

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AU - Hirata, I.

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AU - Itoh, T.

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