Open AccessMolecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre‐ miR‐148a on gene regulation
Author(s) -
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
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13610
Subject(s) - microrna , biology , gene knockdown , cancer research , pancreatic cancer , ectopic expression , oncogene , gene , rna , cancer , gene expression , genetics , cell cycle
We previously used RNA sequencing to establish the micro RNA (mi RNA ) 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 ( PHLDA 2 , LPCAT 2 and AP 1S3 ) and miR‐148a‐3p targets ( SMA , ENDOD1 and UHMK 1 ) was associated with poor prognosis of patients with PDAC. Moreover, knockdown of PHLDA 2 expression inhibited cancer cell aggressiveness, suggesting PHLDA 2 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 mi RNA regulatory networks in lethal PDAC might provide new prognostic markers and therapeutic targets for this disease.