(Pro)renin receptor/ATP6AP2 is required for autophagy and regulates proliferation in lung adenocarcinoma cells

Koji Ohba, Moe Endo, Shigemitsu Sato, Yurina Kashio-Yokota, Takuo Hirose, Kazuhiro Takahashi

研究成果: Article査読

5 被引用数 (Scopus)

抄録

(Pro)renin receptor ((P)RR)/ ATP6AP2 (ATPase, H+ transporting, lysosomal accessory protein 2) functions as an essential accessory subunit of vacuolar H+-ATPase (V-ATPase). V-ATPase is necessary for lysosome function and autophagy. Autophagy is related to cell proliferation, migration and invasion of various cancer cells. In this study, we aim to clarify the relationship between (P)RR and autophagy in lung adenocarcinoma. Expression of (P)RR and Ki-67 (a proliferation marker) was studied in sixty-four adenocarcinoma cases by immunohistochemistry. Lung adenocarcinoma cell line, A549, was transfected with (P)RR-specific siRNA. Autophagy inhibitors, bafilomycin A1 and chloroquine, were used as positive controls. Cell proliferation and migration were measured by WST-8 assay and wound healing assay. Autophagosome markers, p62 and LC3, were analyzed by RT-qPCR, Western blot and immunocytochemistry. Immunohistochemistry showed that (P)RR was expressed in all adenocarcinoma tissues. The intensity of (P)RR immunoreactivity was significantly associated with Ki-67. Treatment of (P)RR-specific siRNA suppressed (P)RR expression and significantly reduced cell proliferation and migration as did the autophagy inhibitors. Western blot and immunocytochemistry showed that (P)RR-specific siRNA, as well as the autophagy inhibitors, induced p62 and LC3 accumulation in cytoplasmic granules. These results suggest that (P)RR is involved in cell proliferation and progression of lung adenocarcinoma via regulating autophagy.

本文言語English
ページ(範囲)782-795
ページ数14
ジャーナルGenes to Cells
25
12
DOI
出版ステータスPublished - 2020 12
外部発表はい

ASJC Scopus subject areas

  • 遺伝学
  • 細胞生物学

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