Polymorphisms and haplotypes of the miR-148/152 family are associated with the risk and clinicopathological features of gastric cancer in a Northern Chinese population

Abstract

Our previous studies showed that the expressions of miR-148a, miR-152 and miR-148b are altered in gastric cancer (GC). The present study aimed to find relationship between individual single nucleotide polymorphisms (SNPs) or haplotypes of these miRNAs and susceptibility, clinicopathological parameters and prognosis of GC in a large sample of the Han population of Northern China. Twelve SNPs were genotyped using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry in a case-control study of 571 Chinese GC patients and 571 cancer-free controls. The rs11170877 G allele (P = 0.027) and the rs12231393 C allele (P = 0.034) were associated with a decreased risk of GC. However, these associations were lost after Bonferroni correction. The rs4719839 G allele was associated with Borrmann type III-IV GC (P = 0.034), increased tumour size (P = 0.020), an increased rate of lymph node metastasis (P = 0.047) and advanced TNM stage (P = 0.009). These associations were also lost after Bonferroni correction. The haplotype of miR-148b was significantly correlated with GC risk. The haplotypes in miRNA-148a were different in Borrmann types. The haplotype of miR-152 distributed various in the positive lymphovascular invasion group compared to negative group. Polymorphisms of miR-148b rs11170877 and 12231393 and their haplotypes were predictive factors of susceptibility to GC. A functional genetic variant of miRNA rs4719839 and the corresponding haplotype were associated with clinicopathological features and prognosis of advanced GCs.

Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre‐miR‐148a on gene regulation

“…In the human genome, the miR-148-family consists of 3 members that are located in different chromosomal regions: miR-148a is at 7p15.2, miR-148b is at 12q13.13 and miR-152 is at 17q21.32. 27,28 The mature sequences of the guide strands of these miRNAs are similar and the seed sequences (UCAGUGCA) are identical. 29 Most analyses have focused on guide strands of the miR-148-family in normal physiological conditions or in cancer cells.…”

Bioinformatics identification of potentially involved microRNAs in Tibetan with gastric cancer based on microRNA profiling

“…Exogenous miR-363 promotes cell growth, progression and tumorsphere formation of SC-M1 gastric cancer cells, and the knockdown of miR-363 suppresses tumorigenesis of SC-M1 cells [ 33 ]. MiR-148a/b is dysregulated and their haplotype is significantly correlated with gastric cancer [ 34 ]. S1PR1 , one of the common targets of miR-148a-3p, -148b-3p and -363-3p, is implicated in NFκB/IL - 6/STAT3/S1PR1 amplification loop that is important for chronic colitis-related cancer and can be suggested as therapeutic option [ 35 ].…”

Inhibition of epithelial‑mesenchymal transition in gastric cancer cells by miR‑711‑mediated downregulation of CD44 expression

“…These findings have demonstrated that miRNAs play a critical role in tumor development, progression and metastasis. The recent development of miRNA microarray analysis of gastric cancer has facilitated the identification of gastric cancer development-, progression-and prognosis-related miRNAs, and includes members of the miR-200 family, miR-27, miR-373, miR-148, miR-129 and miR-711 (12)(13)(14)(15)(16)(17). However, knowledge concerning these miRNAs only represent the tip of the iceberg, as the function of many miRNAs is still unknown.…”