Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre‐miR‐148a on gene regulation. Issue 6 (22nd May 2018)

• Record Type: Journal Article
• Authors: Idichi, Tetsuya; Seki, Naohiko; Kurahara, Hiroshi; Fukuhisa, Haruhi; Toda, Hiroko; Shimonosono, Masataka; Okato, Atsushi; Arai, Takayuki; Kita, Yoshiaki; Mataki, Yuko; kijima, Yuko; Maemura, Kosei; Natsugoe, Shoji
• Is Part Of: Cancer science. Volume 109:Issue 6(2018)
• Page Start: 2013
• Page End: 2026
• Publication Date: 2018-05-22
• Subjects: cancer genome/genetics -- characteristics and pathology of human cancer -- information -- invasion and metastasis -- oncogenes and tumor‐suppressor genes; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13610
• Languages: English
• ISSNs: 1347-9032

Abstract

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. Abstract : Pre‐miR‐148a involved in PDAC pathogenesis.