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Abstract：
In the present study, it was aimed to investigate the effects and potential mechanisms of heat shock protein B7 (HSPB7) on lung adenocarcinoma (LUAD). Bioinformatic analysis was performed to explore the association between HSPB7 expression and patients with LUAD. MTT, colony formation, wound healing and Transwell assays were performed to examine the proliferative, migratory and invasive abilities of H1975 and A549 cells. Western blot analysis was conducted to determine the corresponding protein expression. Co‑Immunoprecipitation and Chromatin immunoprecipitation assays were carried out to reveal the interaction between HSPB7 and myelodysplastic syndrome 1 and ecotropic viral integration site 1 complex locus (MECOM). In addition, an animal model was conducted by the subcutaneous injection of A549 cells into BALB/c nude mice, and tumor weight and size were measured. HSPB7 was downregulated in LUAD tissues and cells, and its expression level correlated with patient prognosis. Cell functional data revealed that silencing of HSPB7 promoted lung cancer cell proliferation, migration, invasion and epithelial mesenchymal transition (EMT); whereas overexpression of HSPB7 led to the opposite results. Furthermore, bioinformatics analysis showed that HSPB7 inhibited glycolysis. HSPB7 decreased glucose consumption, lactic acid production, and lactate dehydrogenase A, hexokinase 2 and pyruvate kinase muscle isoform 2 protein levels. The results demonstrated that MECOM was a transcription factor of HSPB7. Collectively, these results suggested that HSPB7 is regulated by MECOM, and that HSPB7 attenuates LUAD cell proliferation, migration, invasion and EMT by inhibiting glycolysis.
摘要：
在本研究中,目的探讨热休克蛋白B7（HSPB7）对肺腺癌（LUAD）的作用及可能机制。进行生物信息学分析以探讨HSPB7表达与LUAD患者之间的关系。MTT,菌落形成,进行伤口愈合和Transwell测定以检查增殖，H1975和A549细胞的迁移和侵袭能力。进行蛋白质印迹分析以确定相应的蛋白质表达。进行了共免疫沉淀和染色质免疫沉淀测定，以揭示HSPB7与骨髓增生异常综合征1和生态病毒整合位点1复杂基因座（MECOM）之间的相互作用。此外,BALB/c裸鼠皮下注射A549细胞,并测量肿瘤的重量和大小。HSPB7在LUAD组织和细胞中下调，其表达水平与患者预后相关。细胞功能数据显示HSPB7沉默促进肺癌细胞增殖，迁移,侵袭和上皮间质转化（EMT）；而HSPB7的过表达导致相反的结果。此外，生物信息学分析显示HSPB7抑制糖酵解。HSPB7降低葡萄糖消耗，乳酸生产，和乳酸脱氢酶A,己糖激酶2和丙酮酸激酶肌肉同工型2蛋白水平。结果表明MECOM是HSPB7的转录因子。总的来说，这些结果表明HSPB7受MECOM调控，HSPB7减弱LUAD细胞增殖，迁移,通过抑制糖酵解进行侵袭和EMT。
