Genetic variation of miRNA sequence in pancreatic cancer

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs of 20-22 nucleotides (nts) and constitute a novel class of gene regulators that negatively regulate gene expression at the post-transcriptional level. The expression of miRNA is deregulated in many types of cancers. Alterations in miRNA expression may be an important contributor to the development of pancreatic carcinoma. We hypothesized that genetic variations in miRNA genes were associated with pancreatic carcinoma and analyzed genomic sequences coding for the precursors of eight miRNA genes in both pancreatic carcinoma tissues and cancer cell lines. Four novel mutations in primary miRNA transcripts were identified. TaqMan miRNA assays showed that miR-21 was significantly overexpressed in 20 pancreatic carcinomas and 6 cancer cell lines compared with paired benign tissues and normal pancreas. Two mutations of miR-21 did not notably alter the activity of the promoter of the miRNA gene. Although most of these mutations seem to have no effect on miRNA processing, an A-G mutation at 29-nt downstream of pre-miR-21 led to a conformational change of the secondary structure close to the stem reaching into the pre-miR-21 and a relative reduction of the mature miR-21 expression in vivo. These results suggested that miRNA might play an important role in pancreatic tumorigenesis, but the molecular mechanism underlying the particular sequence variations in miRNA that can cause aberrant expression remains to be determined.

Serum MicroRNA Expression Profile as a Biomarker in the Diagnosis and Prognosis of Pancreatic Cancer

“…Previous studies have demonstrated an association between the aberrant miRNA expression and the development of PaC (23)(24)(25)(26); however, these studies mainly focused on miRNAs expressed in tumor tissues and cells. The limitation of tissue miRNAs as a cancer biomarker is that the collection of tissue sample is an invasive procedure.…”

MicroRNA-191 targets <italic>N</italic>-deacetylase/<italic>N</italic>-sulfotransferase 1 and promotes cell growth in human gastric carcinoma cell line MGC803

“…MiR-34b and miR-34c are found to be tumor suppressors frequently silenced by DNA methylation in gastric cancer [14]. Furthermore, genetic variations in miRNA genes were found to be associated with pancreatic cancer [15].…”

New role of microRNA: carcinogenesis and clinical application in cancer

“…For example, in lung cancer, the serological-specific miRNAs include miR-205, miR-206, miR-335, miR-1254, and miR-574-5p [80]; in colorectal cancer, the serological-specific miRNAs include miR-485-5p, miR-361-3p, miR-326, and miR-487b [81,82]; in diffuse large B cell lymphoma, the serological-specific miRNA includes miR-21 [83]. Moreover, in leukemia, patients are shown to have specific circulating miR-92a down-regulated [84]; in metastatic prostate cancer, circulating miR-141 has been significantly elevated in serum [85,86]; in pancreatic cancer, miR-21, miR-155, miR-196a, and miR-210 are all found to be up-regulated in plasma, and miR-196a is confirmed as a new prognostic marker for pancreatic cancer [87][88][89].…”