Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre-miR-148a on gene regulation

Tetsuya Idichi, Naohiko Seki, Hiroshi Kurahara, Haruhi Fukuhisa, Hiroko Toda, Masataka Shimonosono, Atsushi Okato, Takayuki Arai, Yoshiaki Kita, Yuko Mataki, Yuko kijima, Kosei Maemura, Shoji Natsugoe

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

We previously used RNA sequencing to establish the microRNA (miRNA) expression signature of pancreatic ductal adenocarcinoma (PDAC). We found that both strands of pre-miR-148a (miR-148a-5p: the passenger strand and miR-148a-3p: the guide strand) were downregulated in cancer tissues. Ectopic expression of miR-148a-5p and miR-148a-3p significantly inhibited cancer cell migration and invasion, indicating that both strands of pre-miR-148a had tumor-suppressive roles in PDAC cells. In silico database and genome-wide gene expression analyses identified a total of 15 genes that were putative targets regulated by these miRNAs. High expression of miR-148a-5p targets (PHLDA2, LPCAT2 and AP1S3) and miR-148a-3p targets (SMA, ENDOD1 and UHMK1) was associated with poor prognosis of patients with PDAC. Moreover, knockdown of PHLDA2 expression inhibited cancer cell aggressiveness, suggesting PHLDA2 acted as an oncogene in PDAC cells. Involvement of the passenger strand of pre-miR-148a (miR-148-5p) is a new concept in cancer research. Novel approaches that identify tumor-suppressive miRNA regulatory networks in lethal PDAC might provide new prognostic markers and therapeutic targets for this disease.

Original languageEnglish
Pages (from-to)2013-2026
Number of pages14
JournalCancer science
Volume109
Issue number6
DOIs
Publication statusPublished - 06-2018

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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