FAM83A exerts tumor-suppressive roles in cervical cancer by regulating integrins
FAM83A exerts tumor-suppressive roles in cervical cancer by regulating integrins
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FAM83A 通过调节整合素在宫颈癌中发挥肿瘤抑制作用
DOI：
10.3892/ijo.2020.5078
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发表时间：
2020-08-01
影响因子：
5.2
通讯作者：
Lu, Weiguo
中科院分区：
文献类型：
--
作者：
Xu, Junfen;Lu, Weiguo
序列相似家族83成员A （FAM83A）最近被观察到在各种类型的癌症中上调，并被假设为致癌基因。本研究旨在确定FAM83A在宫颈癌中的功能作用及其潜在的分子机制。结果显示，虽然FAM83A在宫颈癌组织中的表达较正常组织升高，但在FIGO晚期、间质浸润深度、分化差和/或淋巴结转移患者中，FAM83A的表达水平降低，且与宫颈癌患者生存时间短呈负相关。FAM83A基因敲低可促进CaSki和HeLa细胞的增殖、迁移和侵袭能力。小鼠异种移植物模型表明，FAM83A敲低可促进体内肿瘤生长。在机制上，RNA测序结果显示，FAM83A的敲低增加了主要与肿瘤发生相关途径相关的基因的转录。此外，FAM83A敲低可提高人宫颈癌组织样品中α1、α3、α5、β4、β5整合素的蛋白水平，且FAM83A的表达与这些蛋白水平呈负相关。综上所述，本研究结果提示FAM83A可能通过抑制整合素的表达在宫颈癌中发挥抑瘤作用，这可能为宫颈癌的生物学基础提供新的认识。
Family with sequence similarity 83 member A (FAM83A) has been recently observed to be upregulated in various types of cancer and hypothesized to be serve as an oncogene. The present study aimed to determine the functional roles and the underlying molecular mechanism of FAM83A in cervical cancer. The results demonstrated that although FAM83A expression was increased in cervical cancer compared with normal tissues, the expression levels of FAM83A were decreased in patients with advanced FIGO stage, deep stromal invasion, poor differentiation and/or lymph node metastasis and negatively associated with short survival time of patients with cervical cancer. FAM83A knockdown promoted cell proliferative, migratory and invasive abilities of CaSki and HeLa cells. A mouse xenograft model demonstrated that FAM83A knockdown promoted tumor growth in vivo. Mechanistically, RNA sequencing results revealed that knockdown of FAM83A increased the transcription of genes mainly associated with oncogenesis-associated pathways. In addition, FAM83A knockdown increased the protein levels of α1, α3, α5, β4 and β5 integrins in vitro and in vivo, and the expression of FAM83A was also negatively associated with the levels of these proteins in human cervical cancer tissue samples. In conclusion, the results of the present study suggested that FAM83A may exert a tumor-suppressive role in cervical cancer by suppressing the expression of integrins, which may offer new insight into the biological basis of cervical cancer.