Department of Thoracic Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China.
Department of Radiation Oncology, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530000, Guangxi Zhuang Autonomous Region, China.
World J Gastroenterol. 2023 Aug 21;29(31):4783-4796. doi: 10.3748/wjg.v29.i31.4783.
Bioinformatics analysis showed that the expression of the poly(A)-specific ribonuclease (PARN) gene in gastric cancer, head and neck squamous cell carcinoma, melanoma, cervical cancer and lung squamous cell carcinoma tissues was significantly higher than that in normal tissues and was associated with high stage and poor prognosis. The expression of the PARN gene in esophageal cancer (EC) tissue is also significantly higher than that in normal tissues, but the effect of PARN on the proliferation, migration and invasion of EC cells remains unclear.
To investigate the relationship between PARN and the proliferation, migration and invasion of EC cells.
The EC tissues of 91 patients after EC surgery and 63 paired precancerous healthy tissues were collected. PARN mRNA levels were measured using a tissue microarray, and the PARN expression level was evaluated using immunohistochemistry to analyze the relationship between PARN expression and clinicopathologic features as well as the survival and prognosis of patients. In addition, the effects of PARN gene knockout on tumor cell proliferation, invasion and migration were studied by using shRNA during the culture of EC cell lines Eca-109 and TE-1, and the effects of the PARN gene on tumor growth were verified by a xenotransplantation nude mice model.
The expression of PARN in EC tissues was higher than that in adjacent normal tissues, and the level of PARN expression was significantly positively correlated with lymphatic metastasis. Patients with high PARN levels had poor overall survival. BIM, IGFBP-5 and p21 levels were significantly increased in the PARN knockout group, while the expression levels of the antiapoptotic proteins Survivin and sTNF-R1 were significantly decreased in the apoptotic antibody array data. In addition, the expression levels of Akt, p-Akt, PIK3CA and CCND1 in the downstream signaling pathway regulating EC progression were significantly decreased. The culture of EC cell lines confirmed that the apoptosis rate of EC cells was significantly increased, the growth and proliferation of tumor cells were significantly inhibited, and the invasion and migration ability of tumor cells were significantly decreased after PARN gene knockout. experiments of BALB/c nude mice transfected with Eca-109 cells expressing control shRNA (sh-NC) and PARN shRNA (sh-PARN) showed that the tumor volume and weight of nude mice treated with sh-PARN were significantly decreased compared with those of nude mice treated with sh-NC, indicating that PARN knockdown significantly inhibited tumor growth .
PARN has antiapoptotic effects on EC cells and promotes their proliferation, invasion and migration, which is associated with the development of EC and poor patient prognosis. PARN may become a potential target for the diagnosis, prognosis prediction and treatment of EC.
生物信息学分析显示，多聚（A）特异性核糖核酸酶（PARN）基因在胃癌、头颈部鳞状细胞癌、黑色素瘤、宫颈癌和肺鳞状细胞癌组织中的表达明显高于正常组织，且与晚期和预后不良有关。PARN 基因在食管癌（EC）组织中的表达也明显高于正常组织，但 PARN 对 EC 细胞增殖、迁移和侵袭的影响尚不清楚。
探讨 PARN 与 EC 细胞增殖、迁移和侵袭的关系。
收集 91 例 EC 手术后患者的 EC 组织和 63 对癌前健康组织的组织微阵列，采用组织微阵列检测 PARN mRNA 水平，采用免疫组织化学法评价 PARN 表达水平，分析 PARN 表达与临床病理特征及患者生存和预后的关系。此外，通过 shRNA 在 EC 细胞系 Eca-109 和 TE-1 的培养中研究 PARN 基因敲除对肿瘤细胞增殖、侵袭和迁移的影响，并通过裸鼠异种移植模型验证 PARN 基因对肿瘤生长的影响。
PARN 在 EC 组织中的表达高于相邻正常组织，PARN 表达水平与淋巴转移显著正相关。PARN 水平高的患者总生存期较差。PARN 基因敲除组中 BIM、IGFBP-5 和 p21 水平明显升高，凋亡抗体阵列数据中抗凋亡蛋白 Survivin 和 sTNF-R1 的表达水平明显降低。此外，调节 EC 进展的下游信号通路中 Akt、p-Akt、PIK3CA 和 CCND1 的表达水平明显降低。EC 细胞系的培养证实，PARN 基因敲除后 EC 细胞的凋亡率明显升高，肿瘤细胞的生长和增殖明显受到抑制，肿瘤细胞的侵袭和迁移能力明显降低。用表达对照 shRNA（sh-NC）和 PARN shRNA（sh-PARN）的 Eca-109 细胞转染 BALB/c 裸鼠的实验表明，与用 sh-NC 处理的裸鼠相比，用 sh-PARN 处理的裸鼠的肿瘤体积和重量明显减小，表明 PARN 敲低显著抑制了肿瘤的生长。
PARN 对 EC 细胞具有抗凋亡作用，并促进其增殖、侵袭和迁移，与 EC 的发生和患者预后不良有关。PARN 可能成为 EC 诊断、预后预测和治疗的潜在靶点。
