Implication of miRNAs in the Pathogenesis of Gallbladder Cancer

Review Article

Austin Biomark Diagn. 2015;2(1): 1014.

Implication of miRNAs in the Pathogenesis of Gallbladder Cancer

Pablo Letelier¹* and Ismael Riquelme²

¹School of Health Sciences, Universidad Católica de Temuco, Chile.

²Department of Pathology, Universidad de La Frontera, CEGIN-BIOREN, Chile.

*Corresponding author: Pablo Letelier, School of Health Sciences, Universidad Católica de Temuco, Manuel Montt 56, Postal Code 4813302, Temuco, Chile

Received: December 10, 2014; Accepted: January 28, 2015; Published: February 02, 2015


MicroRNAs (miRNAs) are small non-coding RNAs which regulate key cellular processes through a negative post-transcriptional regulation of their target mRNAs. They can act either as oncogenes or as tumor suppressors or as both, depending on the specific tissue expression. Oncogenic miRNAs act directly on mRNAs from genes with pro-apoptotic or anti-proliferative roles. Conversely, tumor-suppressor miRNAs repress the expression of genes with oncogenic functions. Deregulation of many of these miRNAs has been associated with tumorigenesis in various cancers and recent studies have shown evidences of abnormal miRNA expression in gallbladder cancer. Here, we review our current understanding of the expression changes in tumor-suppressor miRNAs (miR-1, miR-145, miR-135a-5p, miR-26a, miR-34a, miR-335, miR-130a and miR-218- 5p) and oncogenic miRNAs (miR-155, miR-20a and miR-182) and its implication in the pathogenesis of gallbladder cancer and their potential as diagnostic and prognostic markers.

Keywords: MicroRNAs; Gallbladder cancer; Oncogenes; Tumor suppressors; Diagnostic markers; Prognostic markers

Biogenesis of miRNAs

MicroRNAs (miRNAs) are endogenous non-coding RNAs that bind to the 3’ Untranslated Region (UTR) of a target mRNA, specifically in sequence called MRE (miRNA recognition element) which can be fully or partially complementary. miRNAs are key post-transcriptional regulators of multiple genes and determine the function of the cells under homeostatic and disease conditions [1]. For this reason, are being widely studied as an important family of molecules with promising prospects as diagnostic and prognostic biomarkers and as therapeutic targets [2]. The miRNA genes usually are transcribed by RNA polymerase II or III generating an initial structure, a primary-miRNAs (pri-miRNAs) in the nucleus, with a stem-loop hairpin structure of ~80-nts [3-5]. Mature miRNAs result from cleavage of pri-miRNAs by the Drosha/DGCR8 complex (‘microprocessor’ complex) to form a precursor miRNAs (premiRNA) of a ~60-nts hairpin [6] (Figure 1). Then the pre-miRNA is exported into the cytoplasm by Exportin 5 (XPO5) and Ran-GTP [7]. This pre-miRNA is cleaved by Dicer/TRBP complex generating a miRNA/miRNA* duplex [8]. Finally, one strand of this miRNA duplex binds to the RNA-induced silencing complex (RISC), which carry this strand to target mRNAs, whereas the other strand (miRNA* strand) is degraded [9-11]. However, reports have shown that the temporary string (miRNA*) would have the regulatory capacity, as a mature miRNA [12]. Another processing pathway involves short introns containing miRNA precursors which lack of stem-loop, called “mirtrons”. These miRNA precursors are digested via spliceosome [12,13] and are processed in a Drosha- or Dicer-independent manner. Other reports have stated that many miRNAs can be generated from an unusual hairpin structure which is processed by Ago2 instead of Dicer [14].

Citation: Koc ZP. Thyroglobulin an Informative Marker with Adjunctive FDG PET/CT in Management of Differentiated Thyroid Carcinoma. Austin Biomark Diagn. 2015;2(1): 1013. ISSN: 2378-9867