Overexpressed CA12 has prognostic value in pancreatic cancer and promotes tumor cell apoptosis via NF-κB signaling

• DOI: 10.1007/s00432-020-03447-9
• Publication Date: 2021-01-02T10:03:09Z
• Authors: Yan Du; Zechang Xin; Tongtai Liu; Peng Xu; Feiyu Mao; Jie Yao
• Keywords: Male; 0301 basic medicine; NF-kappa B; Down-Regulation; Apoptosis; Adenocarcinoma; Middle Aged; Prognosis; G1 Phase Cell Cycle Checkpoints; Resting Phase, Cell Cycle; 3. Good health; Gene Expression Regulation, Neoplastic; Pancreatic Neoplasms; 03 medical and health sciences; 0302 clinical medicine; Cell Line, Tumor; Humans; Female; Carbonic Anhydrases; Cell Proliferation; Signal Transduction

Pancreatic adenocarcinoma (PAAD) is among the deadliest forms of cancer globally. Carbonic anhydrase 12 (CA12) is known to play central roles in regulating many cancers, but its function in the context of PAAD is rarely discussed. This study was, therefore, designed to assess the expression of CA12 in PAAD and to explore its underlying mechanistic role in this cancer type.Immunohistochemical staining was used to measure CA12 expression in PAAD samples. The functionality of pancreatic cancer cells expressing varying levels of CA12 was assessed through wound healing, Transwell, and CCK-8 assays. In addition, flow cytometry was used to measure apoptosis and cell cycle progression in these same cells, while Western blotting was used to analyze the expression of proteins associated with the NF-κB signaling pathway.PAAD tissue samples exhibited significant CA12 downregulation (P < 0.001), and lower CA12 expression was, in turn, associated with poorer overall survival (P < 0.001). CA12 overexpression significantly impaired the proliferation of PAAD cell lines, instead inducing their apoptotic death and G0/G1 phase cell cycle arrest (P < 0.05). We additionally found that CA12 may exert its tumor suppressive roles via modulating the NF-κB signaling pathway.These results indicate that CA12 functions as a tumor suppressor in PAAD and may thus be a novel therapeutic target that can be used to guide PAAD patient treatment.