(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.

中文翻译：

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（Pro）肾素受体/ ATP6AP2是自噬所必需的，并调节肺腺癌细胞的增殖,（Pro）肾素受体/ ATP6AP2是自噬所必需的，并调节肺腺癌细胞的增殖

（Pro）肾素受体（（P）RR）/ ATP6AP2（ATPase，H ⁺转运，溶酶体辅助蛋白2）充当液泡H ⁺的必需辅助亚基‐ATPase（V‐ATPase）。V-ATPase是溶酶体功能和自噬所必需的。自噬与各种癌细胞的细胞增殖，迁移和侵袭有关。在这项研究中，我们旨在阐明（P）RR与肺腺癌自噬之间的关系。通过免疫组织化学研究了64例腺癌病例中（P）RR和Ki-67（增殖标记）的表达。用（P）RR特异性siRNA转染肺腺癌细胞A549。自噬抑制剂bafilomycin A1和氯喹用作阳性对照。细胞增殖和迁移通过WST-8测定和伤口愈合测定进行测量。通过RT-qPCR，蛋白质印迹和免疫细胞化学分析了自噬标记物p62和LC3。免疫组织化学显示（P）RR在所有腺癌组织中都有表达。（P）RR免疫反应强度与Ki-67显着相关。（P）RR特异性siRNA的处理与自噬抑制剂一样抑制（P）RR的表达并显着降低细胞增殖和迁移。蛋白质印迹和免疫细胞化学分析显示，（P）RR特异性siRNA以及自噬抑制剂可诱导p62和LC3在细胞质颗粒中积聚。这些结果表明，（P）RR通过调节自噬参与肺腺癌的细胞增殖和进展。诱导p62和LC3在细胞质颗粒中的积累。这些结果表明，（P）RR通过调节自噬参与肺腺癌的细胞增殖和进展。诱导p62和LC3在细胞质颗粒中的积累。这些结果表明，（P）RR通过调节自噬参与肺腺癌的细胞增殖和进展。,（Pro）肾素受体（（P）RR）/ ATP6AP2（ATPase，H ⁺转运，溶酶体辅助蛋白2）充当液泡H ⁺的必需辅助亚基‐ATPase（V‐ATPase）。V-ATPase是溶酶体功能和自噬所必需的。自噬与各种癌细胞的细胞增殖，迁移和侵袭有关。在这项研究中，我们旨在阐明（P）RR与肺腺癌自噬之间的关系。通过免疫组织化学研究了64例腺癌病例中（P）RR和Ki-67（增殖标记）的表达。用（P）RR特异性siRNA转染肺腺癌细胞A549。自噬抑制剂bafilomycin A1和氯喹用作阳性对照。细胞增殖和迁移通过WST-8测定和伤口愈合测定进行测量。通过RT-qPCR，蛋白质印迹和免疫细胞化学分析了自噬标记物p62和LC3。免疫组织化学显示（P）RR在所有腺癌组织中都有表达。（P）RR免疫反应强度与Ki-67显着相关。（P）RR特异性siRNA的处理与自噬抑制剂一样抑制（P）RR的表达并显着降低细胞增殖和迁移。蛋白质印迹和免疫细胞化学分析显示，（P）RR特异性siRNA以及自噬抑制剂可诱导p62和LC3在细胞质颗粒中积聚。这些结果表明，（P）RR通过调节自噬参与肺腺癌的细胞增殖和进展。诱导p62和LC3在细胞质颗粒中的积累。这些结果表明，（P）RR通过调节自噬参与肺腺癌的细胞增殖和进展。诱导p62和LC3在细胞质颗粒中的积累。这些结果表明，（P）RR通过调节自噬参与肺腺癌的细胞增殖和进展。