Down-regulation or loss of MHC class I expression is a major mechanism used by cancer cells to evade immunosurveillance and increase their oncogenic potential. MHC I mediated antigen presentation is a complex regulatory process, controlled by antigen processing machinery (APM) dictating immune response. Transcriptional regulation of the APM that can modulate gene expression profile and their correlation to MHC I mediated antigen presentation in cancer cells remain enigmatic. Here, we reveal that Scaffold/Matrix-Associated Region 1- binding protein (SMAR1), positively regulates MHC I surface expression by down-regulating calnexin, an important component of antigen processing machinery (APM) in cancer cells. SMAR1, a bonafide MAR binding protein acts as a transcriptional repressor of several oncogenes. It is down-regulated in higher grades of cancers either through proteasomal degradation or through loss of heterozygosity (LOH) at the Chr.16q24.3 locus where the human homolog of SMAR1 (BANP) has been mapped. It binds to a short MAR region of the calnexin promoter forming a repressor complex in association with GATA2 and HDAC1. A reverse correlation between SMAR1 and calnexin was thus observed in SMAR1-LOH cells and also in tissues from breast cancer patients. To further extrapolate our findings, influenza A (H1N1) virus infection assay was performed. Upon viral infection, the levels of SMAR1 significantly increased resulting in reduced calnexin expression and increased MHC I presentation. Taken together, our observations establish that increased expression of SMAR1 in cancers can positively regulate MHC I surface expression thereby leading to higher chances of tumor regression and elimination of cancer cells.

中文翻译：

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SMAR1通过调节钙联接蛋白和MHC I表达来促进癌细胞的免疫监测。

MHC I类表达的下调或丧失是癌细胞用来逃避免疫监视并增加其致癌潜能的主要机制。MHC I介导的抗原呈递是一个复杂的调节过程，由指示免疫应答的抗原加工机械（APM）控制。可以调节基因表达谱及其与癌细胞中MHC I介导的抗原呈递的相关性的APM转录调控仍然是一个谜。在这里，我们揭示了支架/基质相关区域1结合蛋白（SMAR1）通过下调钙调蛋白（一种在癌细胞中的抗原加工机械（APM）的重要组成部分）正调控MHC I表面的表达。SMAR1，一种真正的MAR结合蛋白，可作为多种癌基因的转录阻遏物。通过蛋白酶体降解或通过Chr.16q24.3位点的SMAR1（BANP）人类同源物位点的杂合性（LOH）丧失，它在更高级别的癌症中被下调。它与钙粘蛋白启动子的短MAR区结合，形成与GATA2和HDAC1结合的阻遏物复合物。因此，在SMAR1-LOH细胞以及乳腺癌患者的组织中观察到SMAR1和钙联接蛋白之间存在反向相关性。为了进一步推断我们的发现，我们进行了A型流感（H1N1）病毒感染检测。病毒感染后，SMAR1的水平显着增加，导致钙合蛋白表达降低和MHC I呈递增加。在一起