Korean J Gastroenterol.  2012 Jun;59(6):395-400. 10.4166/kjg.2012.59.6.395.

Pancreatic Cancer and MicroRNAs

• Hwang JH

• KMID: 1792843
• DOI: http://doi.org/10.4166/kjg.2012.59.6.395

Abstract

MicroRNAs (miRNAs) are recently discovered non-coding small RNAs that play a role as regulators of genetic expressions in eukaryotic cells. It comprises about 20 nucleotides, which contains seed sequence to bind 3'-untranslated lesion of specific target mRNA. It regulates self-renewal, proliferation and differentiation via post-transcriptional gene slicing in normal situation. Aberrant expressions of miRNAs are observed in many cancers as well. miRNAs in cancer cells have been investigated extensively to have a role in tumorigenesis, invasion, metastasis and chemoresistance. In cancer cells, miRNAs act both as tumor suppressors or oncogenes by doing down-regulation of oncogenes or up-regulation of tumor suppressors, respectively. This suggests miRNAs can be potential therapeutic and diagnostic targets in cancers. Pancreatic cancer is one of the most lethal tumors. In spite of many efforts, overall 5-year survival rate of pancreatic cancer is still very low (<5%). Recently, several miRNAs as an oncomir (acting like oncogenes or tumor suppressor genes) are discovered in pancreatic cancer. Here, the role of miRNAs in pancreatic cancer will be discussed and its possibility of diagnostic/therapeutic target will be also mentioned.

Keyword

Pancreatic neoplasma; MicroRNAs; Epithelial-mesenchymal transition

MeSH Terms

Epithelial-Mesenchymal Transition
Humans
MicroRNAs/*metabolism
Neoplasm Metastasis
Pancreatic Neoplasms/diagnosis/*metabolism
Prognosis

Figure

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  Fig. 1 Biogenesis of microRNAs (miRNAs). Biogenesis of a miRNA begins with the synthesis of pri-miRNA, a long transcript by RNA polymerase II. Pri-miRNA contains 5' cap and 3' poly (A) tail. It is processed to pre-miRNA by Drosha. The pre-miRNA is exported by exportin-5 to the cytoplasm and coverted to mature duplex miRNA by Dicer. Mature miRNA suppress the expression of target mRNA through interaction with the 3'UTR. The specificity of miRNA-mRNA interaction is mainly conferred by 'seed sequence'. RNase III, ribonuclease III; Pri-miRNA, primary miRNA; Pre-miRNA, premature miRNA; ORF, open reading frame; UTR, untranslated region of mRNA; RISC, RNA-induced silencing complex.

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  Fig. 2 Signal pathway of epithelial-mesenchymal transition (EMT). Various signal pathways (Wnt, TGFβ and Notch) activate transcriptional repressors of E-cadherin, such as zinc finger E-box-binding homeobox (ZEB)1/ZEB2, twist and snail and induce EMT. During EMT, phenotypic changes occur from epithelial phenotype to mesenchymal phenotype. EMT plays an essential role in tumor invasion and metastasis. Reverse process-mesenchymal-epithelical transition (MET) may be crucial at metastatic cancer cells colonization. miR-200 family regulates EMT as well, by targeting ZEB1/ZEB2. TGFβ, transforming growth factor β; COX-2, cyclooxygenase-2; IL-6, interleukin-6; miRNA, micro RNA; MMP, matrix metalloproteinase.

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