DNA损伤修复缺陷可导致基因突变,进而诱发癌变.DNA损伤后可以通过染色质重塑复合物引起染色质结构改变,从而帮助损伤的DNA进行修复.SWI/SNF是已知的一种重要的染色质重塑复合物,ARID1A作为该复合物中的一个亚基,是肿瘤抑制因子,在各种肿瘤中存在突变或缺失.对ARID1A的肿瘤抑制作用机制的深入研究,有利于对癌症发生发展机制的深入了解,以期为癌症治疗提供新的靶点.本文对ARID1A的基本特征、在各种癌症中的作用机制,及其生物学作用等进行了综述.

Accumulating evidence has indicated that microRNAs can regulate downstream signaling pathways and play an important role in various tumors. In this study, we found that miR-223-3p was differentially expressed in 40 paired gastric cancer tissues and adjacent tissues and that miR-223-3p was positively correlated with tumor invasion depth and lymph node metastasis. Luciferase reporter assay confirmed that Arid1a was the target gene of miR-223-3p. Functional assays showed that miR-223-3p promoted the proliferation and invasion of gastric cancer cells by regulating the expression of Arid1a. We also confirmed that miR-223-3p regulated the growth of gastric cancer cells in vivo, while an antagomir against miR-223-3p significantly inhibited tumor growth. In conclusion, our results demonstrated that miR-223-3p inhibits gastric cancer cell progression by decreasing the expression of Arid1a. Therefore, miR-223-3p may act as a potential therapeutic target for patients with gastric cancer.

Deletion of the frequently mutated AT-rich interacting domain-containing protein 1A (ARID1A), an SWI/SNF subunit, is associated with poor prognosis in various tumors. This study observed and analyzed ARID1A expression and its correlation with prognosis in gastric carcinoma. Postoperative sections of 98 patients with primary gastric cancer and 40 patients with gastric benign lesions were examined by immunohistochemistry. ARID1A deficiency was observed in 19.39% of gastric cancer tissues, 4.08% of matched paracancerous tissues, and 2.5% of normal gastric mucosa tissues. ARID1A expression was significantly down-regulated in gastric cancer tissues compared with paracancerous tissues (P = .001) and normal gastric mucosa tissues (P = .011). ARID1A deletion significantly correlated with tumor size (P = .022), lymph node metastasis (P = .030), and tumor differentiation (P = .009). In the 90 gastric cancer tissues with tumor stages II and III, the clinical outcome of the ARID1A-negative patients was significantly poorer than that of the ARID1A-positive patients (P = .005). Univariate analysis revealed that tumor invasion depth (P = .025), stage (P = .032), poor differentiation (P = .046), lymph node metastasis (P = .038), and ARID1A expression (P = .023) were significantly related to the overall survival of gastric cancer patients. Multivariate analysis demonstrated that tumor invasion depth (P = .029) and ARID1A expression (P = .031) were independent factors that indicate poor prognosis. In conclusion, the loss of ARID1A expression in gastric cancer patients significantly correlated with poor survival.

Chemotherapy-based comprehensive treatment is the main therapy for advanced gastric cancer (AGC). Although the signifcant progress has been made in the treatment of AGC, the standard first-line chemotherapy regimen for AGC remains controversy due to the low complete response rate of chemotherapy and the short duration of response after chemotherapy. In recent years, with the rapid development of tumor molecular biology, the understanding of various related molecular signaling pathways and the targeted molecules in the occurrence and development of gastric cancer has become clear, this has led to the development of new targeted molecular agents which targeting the critical aspects of oncogenic pathways. DOI:10.3781/j.issn.1000-7431.2015.55.528

Cadherins that mediate the adhesion of the same type of cells by specific binding to calciumdependent adhesions of the same type with cadherins mainly consist of three subtypes including E-cadberin,P-cadherin and N-cadherin.In recent years,more and more studies have indicated that cadherins are closely related to triple-negative breast cancer(TNBC)and play an important role in prognosis and treatment of TNBC.