Department of Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland, Australia; Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi-6205, Bangladesh.
Department of Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast, Queensland, Australia.
Hum Pathol. 2019 May;87:1-10. doi: 10.1016/j.humpath.2018.11.033. Epub 2019 Feb 20.
Family with sequence similarity 134, member B (FAM134B) is an autophagy regulator of endoplasmic reticulum first discovered to be involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). The present study examined the functional behavior of FAM134B in cancer cells and the association of FAM134B expression with clinicopathologic factors in patients with ESCC. Expression at both the mRNA and protein levels was investigated using real-time polymerase chain reaction and immunohistochemistry. The results were correlated with the clinical and pathological features of the patients. In addition, in vitro functional assays were used to investigate the roles of FAM134B in ESCC cells in response to gene silencing with shRNA lentiviral particles. Overexpression of FAM134B mRNA and protein was present in 31.2% (n = 29/93) and 36.6% (n = 41/112), respectively, in tumors, whereas downregulation occurred in 39.8% (n = 37/93) and 63.4% (n = 71/112), respectively. Expression of FAM134B protein in ESCC correlated with histologic grade (P = .002) and pathologic stage (P = .012). In vitro suppression of FAM134B in ESCC induced significant reductions of cell proliferation and colony formation (P < .05). In addition, suppression of FAM134B caused reduction of wound healing, migration, and invasion capacities of ESCC. To conclude, FAM134B could play crucial roles in the initiation and progression of ESCC, and FAM134B protein expression has potential predictive value. Therefore, development of strategies targeting FAM134B could have therapeutic value in the management of patients with ESCC.
家族与序列相似性 134，成员 B（FAM134B）是内质网自噬调节因子，最初发现其参与食管鳞状细胞癌（ESCC）的发病机制。本研究检测了 FAM134B 在癌细胞中的功能行为以及 FAM134B 表达与 ESCC 患者临床病理因素的关系。使用实时聚合酶链反应和免疫组织化学法检测了 mRNA 和蛋白质水平的表达。将结果与患者的临床和病理特征相关联。此外，还使用体外功能测定法研究了 FAM134B 在 ESCC 细胞中的作用，方法是使用 shRNA 慢病毒颗粒对基因沉默进行基因沉默。在肿瘤中，FAM134B mRNA 和蛋白质的过表达分别为 31.2%（n=29/93）和 36.6%（n=41/112），而下调分别为 39.8%（n=37/93）和 63.4%（n=71/112）。ESCC 中 FAM134B 蛋白的表达与组织学分级（P=0.002）和病理分期（P=0.012）相关。在 ESCC 中抑制 FAM134B 表达可显著降低细胞增殖和集落形成（P<0.05）。此外，抑制 FAM134B 还可降低 ESCC 的伤口愈合、迁移和侵袭能力。总之，FAM134B 可能在 ESCC 的发生和发展中发挥关键作用，FAM134B 蛋白表达具有潜在的预测价值。因此，针对 FAM134B 的策略的开发可能对 ESCC 患者的治疗具有治疗价值。
