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Published on: March 30, 2019
CLCA2 suppresses the proliferation, migration and invasion of cervical cancer
Peijin Zhang1, Yang Lin1, Yaqiong Liu2
1Department of Gynecology, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin 300100, P.R. China.
Abstract:
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/β-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.
Insights
Calcium-activated chloride channel A2 (CLCA2) acts as a tumor suppressor in cervical cancer. Lower CLCA2 expression correlates with advanced disease and poorer survival, suggesting it's a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Calcium-activated chloride channel A2 (CLCA2) is a known tumor suppressor implicated in various cancers.
- The role of CLCA2 in human cervical cancer remains largely uncharacterized.
Purpose of the Study:
- To investigate the expression and function of CLCA2 in cervical cancer.
- To determine the association of CLCA2 with clinicopathological features and patient prognosis.
- To explore the potential of CLCA2 as a therapeutic target for cervical cancer.
Main Methods:
- Reverse transcription-quantitative PCR (RT-qPCR) for mRNA expression analysis.
- Immunohistochemistry for protein expression in cervical cancer tissues.
- MTT and Transwell assays to assess cell proliferation and invasion.
- Statistical analysis including Cox regression for survival prediction.
Main Results:
- CLCA2 mRNA and protein expression were significantly decreased in cervical cancer tissues compared to normal tissues.
- Reduced CLCA2 expression correlated with advanced tumor stage, larger tumor size, and HPV infection status.
- CLCA2 upregulation was associated with improved overall and recurrence-free survival.
- CLCA2 knockdown suppressed cervical cancer cell proliferation and migration, implicating its role in Wnt/β-catenin signaling.
Conclusions:
- CLCA2 functions as a tumor suppressor in cervical cancer by inhibiting cell proliferation, migration, and invasion.
- CLCA2 expression levels are a significant prognostic biomarker for cervical cancer patients.
- CLCA2 represents a promising therapeutic target for cervical cancer treatment.
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