Open AccessImpact of novel oncogenic pathways regulated by antitumor miR‐451a in renal cell carcinoma
Author(s) -
Yamada Yasutaka,
Arai Takayuki,
Sugawara Sho,
Okato Atsushi,
Kato Mayuko,
Kojima Satoko,
Yamazaki Kazuto,
Naya Yukio,
Ichikawa Tomohiko,
Seki Naohiko
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.13526
Subject(s) - cancer research , ectopic expression , gene knockdown , cancer , malignancy , microrna , renal cell carcinoma , biology , clear cell renal cell carcinoma , cell , medicine , cell culture , gene , oncology , genetics
Recent analyses of our micro RNA (mi RNA ) expression signatures obtained from several types of cancer have provided novel information on their molecular pathology. In renal cell carcinoma ( RCC ), expression of micro RNA ‐451a ( miR‐451a ) was significantly downregulated in patient specimens and low expression of miR‐451a was significantly associated with poor prognosis of RCC patients ( P = .00305) based on data in The Cancer Genome Atlas. The aims of the present study were to investigate the antitumor roles of miR‐451a and to identify novel oncogenic networks it regulated in RCC cells. Ectopic expression of miR‐451a significantly inhibited cancer cell migration and invasion by RCC cell lines, suggesting that miR‐451a had antitumor roles. To identify oncogenes regulated by miR‐451a in RCC cells, we analyzed genome‐wide gene expression data and examined information in in silico databases. A total of 16 oncogenes and were found to be possible targets of miR‐451a regulation. Interestingly, high expression of 9 genes ( PMM 2 , CRELD 2 , CLEC 2D , SPC 25 , BST 2 , EVL , TBX 15 , DPYSL 3 , and NAMPT ) was significantly associated with poor prognosis. In this study, we focused on phosphomannomutase 2 ( PMM 2 ), which was the most strongly associated with prognosis. Overexpression of PMM 2 was detected in clinical specimens and Spearman's rank test indicated a negative correlation between the expression levels of miR‐451a and PMM 2 ( P = .0409). Knockdown of PMM 2 in RCC cells inhibited cancer cell migration and invasion, indicating overexpression of PMM 2 could promote malignancy. Analytic strategies based on antitumor mi RNA s is an effective tool for identification of novel pathways of cancer.