CLCA2 suppresses the proliferation, migration and invasion of cervical cancer
CLCA2 suppresses the proliferation, migration and invasion of cervical cancer
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DOI：
10.3892/etm.2021.10208
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发表时间：
2021-07-01
影响因子：
2.7
通讯作者：
Liu, Yaqiong
中科院分区：
文献类型：
--
作者：
Zhang, Peijin;Lin, Yang;Liu, Yaqiong
钙激活的氯离子通道A2（CLCA 2）是一种肿瘤抑制因子，与多种癌症的发生有关。然而，很少有人知道CLCA 2在人类宫颈癌。因此，本研究的目的是研究CLCA 2对宫颈癌的影响。应用逆转录-定量（RT-q）PCR方法检测8对宫颈癌组织中CLCA 2 mRNA的表达水平。采用免疫组化法检测144例宫颈癌标本中CLCA 2蛋白的表达。CLCA 2与临床病理参数的关联进行了统计学评估。MTT法检测细胞增殖能力，Transwell法检测细胞侵袭能力。RT-qPCR分析显示，CLCA 2在宫颈癌组织中的表达低于癌旁正常组织。CLCA 2的表达水平与肿瘤分期（P=0.028）、肿瘤大小（P=0.009）和人乳头瘤病毒（HPV）感染状况（P=0.041）相关。此外，CLCA 2上调与手术后较长的总体和无复发生存时间相关（分别为P=0.016和P=0.009）。多因素考克斯回归分析显示，CLCA 2表达对宫颈癌患者的总生存率有预测价值（P=0.017和P=0.025）。通过小干扰RNA敲低CLCA 2抑制肿瘤细胞增殖和迁移。在机制上，CLCA 2参与Wnt/β-连环蛋白信号传导。结论：CLCA 2抑制宫颈癌细胞的增殖、迁移和侵袭，可能成为宫颈癌治疗的潜在靶点。
Ca2+-activated Cl- channel A2 (CLCA2), a tumor suppressor, is associated with the development of several cancers. However, little is known about CLCA2 in human cervical cancer. Therefore, the aim of the present study was to investigate the effects of CLCA2 on cervical cancer. Reverse transcription-quantitative (RT-q)PCR was used to examine the mRNA expression levels of CLCA2 in eight pairs of cervical cancer tissues. Immunohistochemistry was used to investigate CLCA2 protein expression in 144 archived cervical cancer specimens. The association of the CLCA2 with clinicopathological parameters was statistically evaluated. Cell proliferation and invasion capability were examined by MTT and Transwell assays, respectively. RT-qPCR analysis revealed that CLCA2 expression was decreased in cervical cancer compared with that in adjacent normal tissues. The expression levels of CLCA2 in patients were correlated with tumor stage (P=0.028), tumor size (P=0.009), and human papillomavirus (HPV) infection status (P=0.041). In addition, CLCA2 upregulation was associated with longer overall and recurrence-free survival time after surgery (P=0.016 and P=0.009, respectively). Multivariate Cox regression analysis demonstrated that CLCA2 expression had a predictive value for overall survival of patients with cervical cancer (P=0.017 and P=0.025, respectively). Knockdown of CLCA2 by small interfering RNA suppressed tumor cell proliferation and migration. Mechanistically, CLCA2 was involved in Wnt/beta-catenin signaling. In conclusion, the results of the present study demonstrated that CLCA2 suppressed the proliferation, migration and invasion of cervical cancer cells, and that CLCA2 may be a potential therapeutic target of cervical cancer.