Inversin, encoded by NPHP2, is one of the 10 NPHP proteins known to be involved in nephronophthisis (an autosomal recessive cystic kidney). Although the previous reports showed that inversin played an important role in embryonic development and renal diseases, its function in cancer was not revealed clearly so far. As measured by immunohistochemical staining, inversin was highly expressed in the cytoplasm of lung cancer samples (63.4%, 161/254) compared with adjacent normal lung tissues (22.0%, 11/50, p < 0.01). Moreover, its expression was positively correlated with differentiation ( p = 0.014), tumor node metastasis staging ( p = 0.007), and lymph node metastasis ( p = 0.020). The overall survival of non-small cell lung cancer patients with inversin positive expression (45.41 ± 1.800 months) was significantly reduced compared with those with inversin negative expression (51.046 ± 2.238 months, p = 0.042). Consistently, we found that the invasion capacity of A549 cells transfected with inversin was significantly stronger than that of control cells ( p < 0.05), while inversin siRNA-treatment significantly reduced cell invasion in H1299 cells ( p < 0.05). Additionally, we demonstrated that inversin could upregulate the expression of N-cadherin, Vimentin, matrix metalloproteinase-2, and matrix metalloproteinase-9. Collectively, these results indicated that inversin might promote the tumorigenicity of lung cancer cells and serve as a novel therapeutic target of non-small cell lung cancer.

译文

:Inversin由NPHP2编码,是已知与肾小球肾病(常染色体隐性囊性肾)有关的10种NPHP蛋白之一。尽管先前的报道表明,肌钙蛋白在胚胎发育和肾脏疾病中起着重要作用,但到目前为止,其在癌症中的功能尚不清楚。通过免疫组织化学染色测定,与邻近的正常肺组织(22.0%,11/50,p <0.01)相比,转化酶在肺癌样品的细胞质中高表达(63.4%,161/254)。此外,其表达与分化(p = 0.014),肿瘤结转移分期(p = 0.007)和淋巴结转移(p = 0.020)呈正相关。转化蛋白阳性表达的非小细胞肺癌患者(45.41±1.800个月)的总生存期显着低于转化蛋白阴性表达的非小细胞肺癌患者(51.046±2.238 months,p = 0.042)。一致地,我们发现用逆转蛋白转染的A549细胞的侵袭能力明显强于对照细胞(p <0.05),而逆转酶siRNA处理显着降低了H1299细胞的侵袭能力(p <0.05)。此外,我们证明了肌钙蛋白可以上调N-钙黏着蛋白,波形蛋白,基质金属蛋白酶2和基质金属蛋白酶9的表达。总体而言,这些结果表明,肌动蛋白可能促进肺癌细胞的致瘤性,并成为非小细胞肺癌的新型治疗靶标。

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