Department of Integrated Chinese and Western Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Acta Biochim Pol. 2022 Sep 13;69(3):573-578. doi: 10.18388/abp.2020_5867.
The tumour suppressive role of miRNA320a is observed in many cancer types like in colon, lung, breast, and osteosarcoma but it is inversely reported in prostate cancer and in MPM cell lines. miRNA320a targets programmed death ligand 1 (PDL1) negatively in many cancer types and recently in Malignant pleural mesothelioma. In this background it is important to understand the regulatory mechanism of miRNA320a in determining PDL1 expression in different pathological stages of lung cancer. Histology was used to grade the initial and advanced stage of lung cancer following carcinogenic injection. Immunohistochemistry and Western blotting technique were used to analyse PDL1 protein expression. In-situ hybridization was used to determine miRNA320a signals. Initially, using the chemical carcinogen Diethylnitrosamine (25 μg/g), we successfully initiate initial and advanced stage of lung cancer following 6 months and 9 months of carcinogenic injection. The formation of initial and advanced stage of lung cancer is confirmed through histopathological changes which show neoplastic appearance in initial lung cancer and appearance of more mitotic cells along with tissue hardness in the advanced lung cancer stages. In miRNA320a blocked tissue the cancer condition becomes worse with decreased tissue elasticity along with more proliferative cells. Immunohistochemistry and Western blotting studies show that PDL1 is overexpressed in the advanced stages rather than in initial lung cancer because the expression of miRNA320a is overexpressed in initial stages but restricted in advanced stages of lung cancer. miRNA32a blocking studies confirm that miRNA320a expression act as a tumour suppressor that directly controls PDL1 expression that lack of miRNA320a enhances PDL1 expression as well as it triggers lung cancer advances. In summary, miRNA320a possess tumour suppressor function that limits PDL1 expression in initial lung cancer but its control over PDL1 suppression is lost once miRNA320a is downregulated in advanced stage of lung cancer.
miRNA320a 在许多癌症类型中具有肿瘤抑制作用，如结肠癌、肺癌、乳腺癌和骨肉瘤，但在前列腺癌和间皮瘤细胞系中则相反。miRNA320a 在许多癌症类型中负向靶向程序性死亡配体 1（PDL1），最近在恶性胸膜间皮瘤中也是如此。在这种背景下，了解 miRNA320a 在决定肺癌不同病理阶段 PDL1 表达中的调节机制非常重要。组织学用于对致癌注射后肺癌的早期和晚期进行分级。免疫组织化学和 Western blot 技术用于分析 PDL1 蛋白表达。原位杂交用于确定 miRNA320a 信号。最初，使用化学致癌物二乙基亚硝胺（25 μg/g），我们在致癌注射 6 个月和 9 个月后成功地引发了肺癌的早期和晚期。通过组织病理学变化证实了早期和晚期肺癌的形成，这些变化显示出早期肺癌中的肿瘤外观以及晚期肺癌中更多有丝分裂细胞的出现和组织硬度的增加。在 miRNA320a 阻断的组织中，癌症状况变得更糟，组织弹性降低，增殖细胞增多。免疫组织化学和 Western blot 研究表明，PDL1 在晚期阶段过度表达，而不是在早期肺癌中，因为 miRNA320a 的表达在早期阶段过度表达，但在肺癌的晚期阶段受到限制。miRNA32a 阻断研究证实，miRNA320a 表达作为一种肿瘤抑制因子，直接控制 PDL1 的表达，缺乏 miRNA320a 会增强 PDL1 的表达，并促使肺癌进展。总之，miRNA320a 具有肿瘤抑制功能，可限制早期肺癌中 PDL1 的表达，但一旦 miRNA320a 在晚期肺癌中下调，其对 PDL1 抑制的控制就会丢失。
