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MicroRNA-10a is Overexpressed in Human Pancreatic Cancer and Involved in Its Invasiveness Partially via Suppression of the HOXA1 Gene

Kenoki Ohuchida MD, PhD, Kazuhiro Mizumoto MD, PhD, Cui Lin MD, PhD, Hiroshi Yamaguchi MD, PhD, Takao Ohtsuka MD, PhD, Norihiro Sato MD, PhD, Hiroki Toma MD, PhD, Masafumi Nakamura MD, PhD, Eishi Nagai MD, PhD, Makoto Hashizume MD, PhD, Masao Tanaka MD, PhD
Pancreatic Tumors
Volume 19, Issue 7 / July , 2012

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.

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