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

由NPHP2编码的Inversin是已知参与肾炎 (常染色体隐性遗传性囊性肾脏) 的10种NPHP蛋白之一。尽管先前的报道表明,invers素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。免疫组织化学染色显示,与癌旁正常肺组织 (22.0% 、11/50、p  <  0.01) 相比,肺癌标本 (63.4% 、161/254) 胞浆中inversin高表达。其表达与分化程度 (p   =   0.014) 、淋巴结转移分期 (p   =   0.007) 、淋巴结转移 (p   =   0.020) 呈正相关。非小细胞肺癌患者中,inversin阳性表达 (45.41   ±   1.800  个月) 的总生存期明显低于inversin阴性表达 (51.046   ±   2.238  个月,p   =   0.042)。一致地,我们发现用逆转录蛋白转染的A549细胞的侵袭能力明显强于对照细胞 (p  <  0.05),而逆转录蛋白siRNA处理显著降低H1299细胞的细胞侵袭能力 (p  <  0.05)。此外,我们证明了inversin可以上调N-钙粘蛋白,波形蛋白,基质metalloproteinase-2和基质metalloproteinase-9的表达。总之,这些结果表明,inversin可能促进肺癌细胞的致瘤性,并可作为非小细胞肺癌的新治疗靶标。

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