BRM (BRAHMA) is a core, SWI2/SNF2-type ATPase subunit of SWI/SNF chromatin-remodelling complex (CRC) involved in various important regulatory processes including development. Mutations in SMARCA2, a BRM-encoding gene as well as overexpression or epigenetic silencing were found in various human diseases including cancer. Missense mutations in SMARCA2 gene were recently connected with occurrence of Nicolaides–Baraitser genetics syndrome. By contrast, SMARCA2 duplication rather than mutations is characteristic for Coffin–Siris syndrome. It is believed that BRM usually acts as a tumour suppressor or a tumour susceptibility gene. However, other studies provided evidence that BRM function may differ depending on the cancer type and the disease stage, where BRM may play a role in the disease progression. The existence of alternative splicing forms of SMARCA2 gene, leading to appearance of truncated functional, loss of function or gain-of-function forms of BRM protein suggest a far more complicated mode of BRM-containing SWI/SNF CRCs actions. Therefore, the summary of recent knowledge regarding BRM alteration in various types of cancer and highlighting of differences and commonalities between BRM and BRG1, another SWI2/SNF2 type ATPase, will lead to better understanding of SWI/SNF CRCs function in cancer development/progression. BRM has been recently proposed as an attractive target for various anticancer therapies including the use of small molecule inhibitors, synthetic lethality induction or proteolysis-targeting chimera (PROTAC). However, such attempts have some limitations and may lead to severe side effects given the homology of BRM ATPase domain to other ATPases, as well as due to the tissue-specific appearance of BRM- and BRG1-containing SWI/SNF CRC classes. Thus, a better insight into BRM-containing SWI/SNF CRCs function in human tissues and cancers is clearly required to provide a solid basis for establishment of new safe anticancer therapies.

中文翻译：

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BRM：SWI / SNF染色质重塑复合物的核心ATPase亚基是肿瘤抑制因子还是肿瘤促进因子？

BRM（BRAHMA）是SWI / SNF染色质重塑复合体（CRC）的核心SWI2 / SNF2型ATPase亚基，参与各种重要的调控过程，包括开发。在包括癌症在内的各种人类疾病中发现了SMARCA2（BRM编码基因）突变以及过表达或表观遗传沉默。SMARCA2基因的错义突变最近与Nicolaides-Baraitser遗传综合症的发生有关。相比之下，SMARCA2复制而不是突变是Coffin-Siris综合征的特征。据信，BRM通常充当肿瘤抑制基因或肿瘤易感基因。但是，其他研究提供的证据表明，BRM的功能可能因癌症类型和疾病阶段而异，其中BRM可能在疾病进展中起作用。SMARCA2基因的其他剪接形式的存在，导致BRM蛋白的功能被截断，功能丧失或功能获得形式出现，表明含BRM的SWI / SNF CRC的作用方式要复杂得多。因此，有关各种癌症中BRM改变的最新知识的总结以及强调另一种SWI2 / SNF2型ATPase BRM和BRG1之间的差异和共性，将使人们更好地理解SWI / SNF CRC在癌症发展/进展中的功能。最近，BRM被提出作为各种抗癌疗法的有吸引力的靶标，包括使用小分子抑制剂，合成致死诱导或靶向蛋白水解的嵌合体（PROTAC）。然而，鉴于BRM ATPase结构域与其他ATPase的同源性以及含BRM和BRG1的SWI / SNF CRC类的组织特异性外观，此类尝试存在一定局限性，并且可能导致严重的副作用。因此，显然需要更好地了解含BRM的SWI / SNF CRC在人体组织和癌症中的功能，以为建立新的安全抗癌疗法提供坚实的基础。