E-cadherin Downregulation and microRNAs in Sporadic Intestinal-Type Gastric Cancer

Abstract

CDH1 gene, encoding E-cadherin, is a tumor suppressor gene frequently altered in gastric cancers (GCs) of both diffuse (DGC) and intestinal (IGC) histotypes, albeit through different mechanisms. The study aimed to characterize CDH1 expression in sporadic IGC and to investigate whether microRNAs (miRs) are involved in its transcriptional control. We evaluated CDH1 expression by quantitative real-time PCR (RT-qPCR) in 33 IGC patients and found a significant downregulation in tumor tissues compared to normal counterparts (p-value = 0.025). Moreover, 14 miRs, predicted to be involved in CDH1 regulation in both a direct and indirect manner, were selected and analyzed by RT-qPCR in an independent case series of 17 IGCs and matched normal tissues. miR-101, miR-26b, and miR-200c emerged as significantly downregulated and were confirmed in the case series of 33 patients (p-value < 0.001). Finally, we evaluated EZH2 expression, a target of both miR-101 and miR-26b, which showed significant upregulation in IGCs (p-value = 0.005). A significant inverse correlation was observed between EZH2 overexpression and CDH1, miR-101, and miR-26b levels (p-value < 0.001). Our results reinforce the link between CDH1 and IGC, highlighting the role of miRs in its transcriptional control and improving our understanding of GC subtypes and biomarkers.

Role of Cadherins in Cancer—A Review

“…The role of cadherins in the process of cancer development has been studied widely over the last decades [ 6 , 10 , 11 , 12 ]. In human medicine, cadherins have been evaluated in many malignancies, such as pancreatic cancer, melanoma, hepatocellular carcinoma, glioblastoma, breast and gastric cancers [ 13 , 14 , 15 , 16 ]. Because most of humans’ solid tumors are of epithelial origin, adhesion molecules at the junctions of epithelial cells and cell signaling pathways are of great interest.…”

Serum miR-101-3p combined with pepsinogen contributes to the early diagnosis of gastric cancer

“…MiR-101 acts as a tumor suppressor in GC. The expression of miR-101 in GC tissues was significantly decreased compared with adjacent normal tissues [9][10][11]. Dong X et al have proved that miR-101 is an independent prognostic factor for the overall survival of GC patients that correlated with the pathological differentiation degree, lymph node metastasis and depth of infiltration [10].…”

“…Dong X et al have proved that the expression of miR-101 in GC tissues is significantly lower than that in cancer-adjacent normal tissues, and miR-101 is an independent prognostic factor affecting the overall survival of GC patients [10]. Rossi T et al have shown that miR-101 is significantly down-regulated in 33 patients with intestinal GC [11]. In addition to that in tumor tissues, the expression of miR-101 in plasma is also a sensitive indicator for GC.…”

The role of histone methylation in the development of digestive cancers: a potential direction for cancer management

“…18 In addition, loss of miR-26, miR-101, and miR-214 contributes to overexpression of EZH2, leading to the development of digestive cancers. [19][20][21][22][23] Among the abovementioned microRNAs, the effect of miR-26 on EZH2 has been widely noted and has been identified in HCC, CRC, and GC. 19,20,22 Another study identified that EZH2 can also bind to the lncRNA HOX-AS2 together with KDM1A to form a complex implicated in PC cell proliferation, 24 and a similar function can also be performed by the lncRNA HOXA11-AS in GC.…”