Expression of the CLCA4 Gene in Esophageal Carcinoma and Its Impact on the Biologic Function of Esophageal Carcinoma Cells

Abstract

Background. Esophageal carcinoma (ESCA) is one of the malignant tumors with a high mortality rate worldwide, which seriously affects people’s health. Calcium-activated chloride channel 4 (CLCA4) was reported to be a tumor inhibitor in hepatocellular carcinoma. Nevertheless, the role of CLCA4 in ESCA is still unclear. Methods. RT-qPCR and western blot assay were used to test the expression pattern of CLCA4 in ESCA tissues and cells. CCK-8 assay was performed to detect the effect of CLCA4 overexpression on cell proliferation in ESCA cells. Transwell assay was used to measure the effect of CLCA4 upregulation on migration and invasion abilities of ESCA cells. Animal experiments were conducted to investigate the role of CLCA4 upregulation in tumor growth in vivo. Results. CLCA4 was significantly reduced in ESCA tissues and correlated with T stage, differentiation, and lymph node metastasis. CLCA4 overexpression was found to inhibit cell proliferation, migration, invasion, and EMT progression in ESCA cells. Moreover, CLCA4 overexpression suppressed tumor growth in vivo. Conclusion. CLCA4 was suggested to act as a tumor inhibitor in ESCA and might be a therapeutic target gene for the treatment of patients with ESCA.

Construction of a new prognostic model for colorectal cancer based on bulk RNA-seq combined with The Cancer Genome Atlas data

“…Subsequently, we conducted LASSO analysis and ultimately selected seven biomarkers ( RETNLB , CLCA4 , UGT2A3 , SULT1B1 , CCL24 , BMP5 , and ATOH1 ) for constructing a prognostic risk model. According to existing literature reports, RETNLB is a tumor promoter in oral squamous cell carcinoma and is significantly correlated with poor prognosis in CRC patients ( 33 ); CLCA4 can reduce the proliferation, migration, and invasion of CRC cells by inhibiting the PI3K/AKT pathway ( 34 - 36 ); CLCA4 serves as a tumor suppressor in esophageal cancer ( 37 ), but promotes tumor development in head and neck squamous cell carcinoma ( 38 ); UGT2A3 inhibits the proliferation and metastasis of CRC cells ( 39 ); similarly, SULT1B1 is a distinct biomarker for CRC ( 40 ); CCL24 promotes the occurrence of various cancers, including CRC, non-small cell carcinoma, and nasopharyngeal carcinoma, through M2 macrophage polarization, angiogenesis, invasion and migration, and eosinophil recruitment ( 41 ); BMP5 induces a reduction in migration and invasion of breast cancer cells ( 42 ), and BMP5 gene deletion delays the occurrence of prostate cancer and skin cancer in mice ( 43 ); ATOH1 has been less studied in the mechanism of cancer, but its association with intestinal health has been identified.…”

Differential Gene Expression of Checkpoint Markers and Cancer Markers in Mouse Models of Spontaneous Chronic Colitis

“…In fact, it was noted that the downregulation of CLCA4 expression correlates to the progression of CRC, breast cancer, stomach cancer, and head and neck cancers [112]. Further, CLCA4 is significantly reduced in oesophageal cancer tissues, and its expression correlates with stage, differentiation, lymph node involvement, and metastatic disease [113]. Transporter associated with antigen processing 1 (Tap1) was significantly overexpressed in both Winnie (log fc 2.7) and Winnie-Prolapse (log fc 3.3) mice, associated with antigen processing and presentation pathways.…”

Approach for Elucidating the Molecular Mechanism of Epithelial to Mesenchymal Transition in Fibrosis of Asthmatic Airway Remodeling Focusing on Cl− Channels

“…In contrast, knockdown of CLCA2 has the opposite effect [ 76 ]. Furthermore, CLCA4 has also been reported to suppress EMT in esophageal cancer, colorectal cancer, liver cancer, and breast cancer by regulating specific signaling pathways such as the PI3K/AKT pathway [ 77 , 78 , 79 , 80 ]. These results indicate that the Ca 2+ -dependent Cl − channels CLCA1, CLCA2, and CLCA4 function as tumor suppressors.…”