Abstract：
BACKGROUND: CELF2 belongs to the CELF RNA-binding protein family and exhibits antitumor activity in various tumor models. Analysis of the pan-cancer TCGA database reveals that CELF2 expression strongly correlates with favorable prognosis among cancer patients. The function of CELF2 in nonmelanoma skin cancer has not been studied.
METHODS: We used shRNA-mediated knockdown (KD) of CELF2 expression in human squamous cell carcinoma (SCC) cells to investigate how CELF2 impacted SCC cell proliferation, survival, and xenograft tumor growth. We determined CELF2 expression in human SCC tissues and adjacent normal skin using immunofluorescence staining. Additionally, we investigated the changes in CELF2 and its target gene expression during UV-induced and chemical-induced skin tumorigenesis by western blotting.
RESULTS: CELF2 KD significantly increased SCC cell proliferation, colony growth, and SCC xenograft tumor growth in immunodeficient mice. CELF2 KD in SCC cells led to activation of KRT80 and GDF15, which can potentially promote cell proliferation and tumor growth. While control SCC cells were sensitive to anticancer drugs such as doxorubicin, SCC cells with CELF2 KD became resistant to drug-induced tumor growth retardation. Finally, we found CELF2 expression diminished during both UV- and chemical-induced skin tumorigenesis in mice, consistent with reduced CELF2 expression in human SCC tumors compared to adjacent normal skin.
CONCLUSIONS: This study shows for the first time that CELF2 loss occurs during skin tumorigenesis and increases drug resistance in SCC cells, highlighting the possibility of targeting CELF2-regulated pathways in skin cancer prevention and therapies.
METHODS: We used shRNA-mediated knockdown (KD) of CELF2 expression in human squamous cell carcinoma (SCC) cells to investigate how CELF2 impacted SCC cell proliferation, survival, and xenograft tumor growth. We determined CELF2 expression in human SCC tissues and adjacent normal skin using immunofluorescence staining. Additionally, we investigated the changes in CELF2 and its target gene expression during UV-induced and chemical-induced skin tumorigenesis by western blotting.
RESULTS: CELF2 KD significantly increased SCC cell proliferation, colony growth, and SCC xenograft tumor growth in immunodeficient mice. CELF2 KD in SCC cells led to activation of KRT80 and GDF15, which can potentially promote cell proliferation and tumor growth. While control SCC cells were sensitive to anticancer drugs such as doxorubicin, SCC cells with CELF2 KD became resistant to drug-induced tumor growth retardation. Finally, we found CELF2 expression diminished during both UV- and chemical-induced skin tumorigenesis in mice, consistent with reduced CELF2 expression in human SCC tumors compared to adjacent normal skin.
CONCLUSIONS: This study shows for the first time that CELF2 loss occurs during skin tumorigenesis and increases drug resistance in SCC cells, highlighting the possibility of targeting CELF2-regulated pathways in skin cancer prevention and therapies.
摘要：
背景：CELF2属于CELFRNA结合蛋白家族，在各种肿瘤模型中表现出抗肿瘤活性。泛癌症TCGA数据库的分析揭示了CELF2表达与癌症患者的良好预后密切相关。尚未研究CELF2在非黑色素瘤皮肤癌中的功能。
方法：我们使用shRNA介导的人鳞状细胞癌（SCC）细胞中CELF2表达的敲低（KD）来研究CELF2如何影响SCC细胞增殖，生存,和异种移植肿瘤生长。我们使用免疫荧光染色确定了CELF2在人SCC组织和邻近正常皮肤中的表达。此外,我们通过蛋白质印迹法研究了在紫外线诱导和化学诱导的皮肤肿瘤发生过程中CELF2及其靶基因表达的变化。
结果：CELF2KD显著增加SCC细胞增殖，菌落生长，和免疫缺陷小鼠中SCC异种移植肿瘤的生长。SCC细胞中的CELF2KD导致KRT80和GDF15的激活，这可能潜在地促进细胞增殖和肿瘤生长。而对照SCC细胞对抗癌药物如多柔比星敏感，具有CELF2KD的SCC细胞对药物诱导的肿瘤生长迟缓产生抗性。最后,我们发现CELF2表达在UV和化学诱导的小鼠皮肤肿瘤发生过程中减少，与邻近正常皮肤相比，人SCC肿瘤中CELF2表达降低。
结论：这项研究首次表明，在皮肤肿瘤发生过程中，CELF2丢失发生，并增加SCC细胞的耐药性，强调在皮肤癌预防和治疗中靶向CELF2调节途径的可能性。
方法：我们使用shRNA介导的人鳞状细胞癌（SCC）细胞中CELF2表达的敲低（KD）来研究CELF2如何影响SCC细胞增殖，生存,和异种移植肿瘤生长。我们使用免疫荧光染色确定了CELF2在人SCC组织和邻近正常皮肤中的表达。此外,我们通过蛋白质印迹法研究了在紫外线诱导和化学诱导的皮肤肿瘤发生过程中CELF2及其靶基因表达的变化。
结果：CELF2KD显著增加SCC细胞增殖，菌落生长，和免疫缺陷小鼠中SCC异种移植肿瘤的生长。SCC细胞中的CELF2KD导致KRT80和GDF15的激活，这可能潜在地促进细胞增殖和肿瘤生长。而对照SCC细胞对抗癌药物如多柔比星敏感，具有CELF2KD的SCC细胞对药物诱导的肿瘤生长迟缓产生抗性。最后,我们发现CELF2表达在UV和化学诱导的小鼠皮肤肿瘤发生过程中减少，与邻近正常皮肤相比，人SCC肿瘤中CELF2表达降低。
结论：这项研究首次表明，在皮肤肿瘤发生过程中，CELF2丢失发生，并增加SCC细胞的耐药性，强调在皮肤癌预防和治疗中靶向CELF2调节途径的可能性。
