Department of General Surgery, Drum Tower Clinical Medical College of Nanjing Medical University, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, People's Republic of China.
Department of Gastrointestinal, Xuzhou Central Hospital, Affiliated Central Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
J Transl Med. 2022 Jul 21;20(1):327. doi: 10.1186/s12967-022-03525-1.
Recent studies have shown that the fox family plays a vital role in tumorigenesis and progression. Forkhead Box S1 (FOXS1), as a newly identified subfamily of the FOX family, is overexpressed in certain types of malignant tumors and closely associated with patient's prognosis. However, the role and mechanism of the FOXS1 in colorectal cancer (CRC) remain unclear.
FOXS1 level in CRC tissues and cell lines was analyzed by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) was used to detect the relationship between FOXS1 expression and clinicopathological features in 136 patients in our unit. The expression of FOXS1 was knocked down in CRC cells using small interfering RNA (siRNA) technology. Cell proliferation was assessed by CCK8 assay, colony formation, and 5-Ethynyl-20-deoxyuridine (EdU) incorporation assay. Flow cytometry detected apoptosis and wound healing, and Transwell assays determined cell migration and invasion. Western blotting was used to detect the levels of proteins associated with the Wnt/β-catenin signaling pathway. Then, we used short hairpin RNA (shRNA) to knock down FOXS1 to see the effect of FOXS1 on the proliferation, migration, invasion, and metastasis of CRC cells in vivo. Finally, we investigated the impact of Wnt activator LiCl on the proliferation, migration, invasion, and metastasis of CRC cells after FOXS1 knockdown.
Compared to those in normal groups, FOXS1 overexpressed in CRC tissues and CRC cells (P < 0.05). Upregulation of FOXS1 association with poor prognosis of CRC patients. si-FOXS1 induced apoptosis and inhibited proliferation, migration, invasion, the epithelial-mesenchymal transition (EMT), and the Wnt/β-catenin signaling pathway in vitro; sh-FOXS1 inhibited the volume and weight of subcutaneous xenografts and the number of lung metastases in vivo. LiCl, an activator of Wnt signaling, partially reversed the effect of FOXS1 overexpression on CRC cells.
FOXS1 could function as an oncogene and promote CRC cell proliferation, migration, invasion and metastasis through the Wnt/βcatenin signaling pathway, FOXS1 may be a potential target for CRC treatment.
最近的研究表明，狐狸家族在肿瘤发生和进展中起着至关重要的作用。叉头框 S1（FOXS1）作为 FOX 家族的一个新发现的亚家族，在某些类型的恶性肿瘤中过度表达，并与患者的预后密切相关。然而，FOXS1 在结直肠癌（CRC）中的作用和机制尚不清楚。
通过 Western blot 和定量实时聚合酶链反应（qRT-PCR）分析 CRC 组织和细胞系中的 FOXS1 水平。免疫组织化学（IHC）检测本单位 136 例患者中 FOXS1 表达与临床病理特征的关系。采用小干扰 RNA（siRNA）技术敲低 CRC 细胞中的 FOXS1 表达。通过 CCK8 测定、集落形成和 5-乙炔基-20-脱氧尿苷（EdU）掺入测定评估细胞增殖。流式细胞术检测细胞凋亡，划痕愈合和 Transwell 测定检测细胞迁移和侵袭。Western blot 检测与 Wnt/β-catenin 信号通路相关的蛋白水平。然后，我们使用短发夹 RNA（shRNA）敲低 FOXS1，观察 FOXS1 对 CRC 细胞体内增殖、迁移、侵袭和转移的影响。最后，我们研究了 Wnt 激活剂 LiCl 对 FOXS1 敲低后 CRC 细胞增殖、迁移、侵袭和转移的影响。
与正常组相比，CRC 组织和 CRC 细胞中 FOXS1 过度表达（P<0.05）。FOXS1 上调与 CRC 患者预后不良相关。体外 si-FOXS1 诱导细胞凋亡，抑制增殖、迁移、侵袭、上皮-间充质转化（EMT）和 Wnt/β-catenin 信号通路；体内 sh-FOXS1 抑制皮下异种移植的体积和重量以及肺转移的数量。Wnt 信号的激活剂 LiCl 部分逆转了 FOXS1 过表达对 CRC 细胞的影响。
FOXS1 可作为癌基因，通过 Wnt/β-catenin 信号通路促进 CRC 细胞增殖、迁移、侵袭和转移，FOXS1 可能成为 CRC 治疗的潜在靶点。
