MicroRNA-10a is overexpressed in human pancreatic cancer and involved in its invasiveness partially via suppression of the HOXA1 gene

Kenoki Ohuchida, Kazuhiro Mizumoto, Cui Lin, Hiroshi Yamaguchi, Takao Ohtsuka, Norihiro Sato, Hiroki Toma, Masafumi Nakamura, Eishi Nagai, Makoto Hashizume, Masao Tanaka

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Abstract

Background. There is increasing evidence that microRNAs are differentially expressed in many types of cancers. Despite progress in analyses of microRNAs in several types of cancers, the functional contributions of microRNAs to pancreatic cancer remain unclear. Methods. In the present study, the expression levels of specific microRNAs identified by microarray analyses were examined in a panel of 15 pancreatic cancer cell lines. We then investigated the functional roles of these microRNAs in the proliferation and invasion of pancreatic cancer cells. Results. Based on the microarray data, we found frequent and marked overexpression of miR-10a, miR-92, and miR- 17-5p in pancreatic cancer cell lines. Microdissection analyses revealed that miR-10a was overexpressed in pancreatic cancer cells isolated from a subset of primary tumors (12 of 20, 60%) compared with precursor lesions and normal ducts (P<.01). In vitro experiments revealed that miR-10a inhibitors decreased the invasiveness of pancreatic cancer cells (P<.01), but had no effect on their proliferation. Inhibition of HOXA1, a target of miR-10a, promoted the invasiveness of pancreatic cancer cells (P<.01). Conclusions. The present data suggest that miR-10a is overexpressed in a subset of pancreatic cancers and is involved in the invasive potential of pancreatic cancer cells partially via suppression of HOXA1.

Original languageEnglish
Pages (from-to)2394-2402
Number of pages9
JournalAnnals of Surgical Oncology
Volume19
Issue number7
DOIs
Publication statusPublished - Jul 1 2012

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MicroRNAs
Pancreatic Neoplasms
Genes
Cell Line
Neoplasms
Microdissection
Microarray Analysis

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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MicroRNA-10a is overexpressed in human pancreatic cancer and involved in its invasiveness partially via suppression of the HOXA1 gene. / Ohuchida, Kenoki; Mizumoto, Kazuhiro; Lin, Cui; Yamaguchi, Hiroshi; Ohtsuka, Takao; Sato, Norihiro; Toma, Hiroki; Nakamura, Masafumi; Nagai, Eishi; Hashizume, Makoto; Tanaka, Masao.

In: Annals of Surgical Oncology, Vol. 19, No. 7, 01.07.2012, p. 2394-2402.

Research output: Contribution to journalArticle

Ohuchida, Kenoki ; Mizumoto, Kazuhiro ; Lin, Cui ; Yamaguchi, Hiroshi ; Ohtsuka, Takao ; Sato, Norihiro ; Toma, Hiroki ; Nakamura, Masafumi ; Nagai, Eishi ; Hashizume, Makoto ; Tanaka, Masao. / MicroRNA-10a is overexpressed in human pancreatic cancer and involved in its invasiveness partially via suppression of the HOXA1 gene. In: Annals of Surgical Oncology. 2012 ; Vol. 19, No. 7. pp. 2394-2402.
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AU - Lin, Cui

AU - Yamaguchi, Hiroshi

AU - Ohtsuka, Takao

AU - Sato, Norihiro

AU - Toma, Hiroki

AU - Nakamura, Masafumi

AU - Nagai, Eishi

AU - Hashizume, Makoto

AU - Tanaka, Masao

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AB - Background. There is increasing evidence that microRNAs are differentially expressed in many types of cancers. Despite progress in analyses of microRNAs in several types of cancers, the functional contributions of microRNAs to pancreatic cancer remain unclear. Methods. In the present study, the expression levels of specific microRNAs identified by microarray analyses were examined in a panel of 15 pancreatic cancer cell lines. We then investigated the functional roles of these microRNAs in the proliferation and invasion of pancreatic cancer cells. Results. Based on the microarray data, we found frequent and marked overexpression of miR-10a, miR-92, and miR- 17-5p in pancreatic cancer cell lines. Microdissection analyses revealed that miR-10a was overexpressed in pancreatic cancer cells isolated from a subset of primary tumors (12 of 20, 60%) compared with precursor lesions and normal ducts (P<.01). In vitro experiments revealed that miR-10a inhibitors decreased the invasiveness of pancreatic cancer cells (P<.01), but had no effect on their proliferation. Inhibition of HOXA1, a target of miR-10a, promoted the invasiveness of pancreatic cancer cells (P<.01). Conclusions. The present data suggest that miR-10a is overexpressed in a subset of pancreatic cancers and is involved in the invasive potential of pancreatic cancer cells partially via suppression of HOXA1.

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