Bladder cancer: Micro RNAs as biomolecules for prognostication and surveillance

Abstract

Introduction:Bladder cancer (BC) has varied clinical behavior in terms of recurrence and progression. Current pathological characteristics are insufficient to prognosticate the outcome of a given treatment. Cellular metabolic regulatory molecules, such as micro RNA (miRNA), could be a potential biomarker to prognosticate the treatment outcomes.Materials and Methods:PubMed and Google Scholar databases were searched for publications from 1990 to 2016, related to miRNA biogenesis, its function, and role in the pathogenesis of bladder as well as other cancers. Articles were searched using MeSH terms micrornas, micrornas AND neoplasm, and micrornas AND urinary bladder neoplasm. Out of the 108 publications reviewed 75 references were selected based on the clinical relevance. Articles were reviewed to assess the role of miRNA in various cancers and those in BC as a diagnostic or therapeutic tool.Results:More than 35 miRNAs were found to be associated with different pathways of cellular dedifferentiation, proliferation, and progression of BC as well as other cancers. A normal looking mucosa may show molecular changes preceding phenotypic changes in the form of varied expression of miR-129, miR-200a, and miR-205. miR-214, miR-99a, and miR-125b have been shown to be potential urinary biomarkers of BC. miRNAs could act as a repressor for protein molecule functioning or activator of different pathways to be used as a therapeutic target too.Conclusions:Despite certain limitations, such as instability, rapid plasma clearance, and targeting antagonist proteins of cellular metabolic pathways, miRNAs have potential to be studied as a biomarker or a therapeutic target for BC.

Role of Non-Coding RNAs in the Etiology of Bladder Cancer

“…However, in most of these studies, only the deregulation of miR is considered, without any clue about the miR role in BC etiology. A recent meta-analysis performed by searching the PubMed and Google Scholar databases for publications ranging between 1990 and 2016 allowed identifying at least 35 miR specifically associated with different pathways of cellular dedifferentiation, proliferation, and progression of BC as well as of other cancers [ 184 ]. In this review, we have focused only on miR with an established role in urothelium neoplastic transformation by means of at least one identified target gene ( Table 3 ) and have discussed only a few of them as prominent examples.…”

“…Therefore, miR-205 is possibly involved in many biochemical processes, including carcinogenesis. miR-205 may act as a diagnostic and prognostic BC marker, since it has been discovered that a mucosa with a normal appearance may have molecular changes (that precede phenotypic changes) in the form of varied expression of this molecule, besides other miR, such as miR-129 and miR-200a [ 184 ]. miR-21 targets many genes that can be involved in the formation and development of cancer, including TP53 [ 207 ], PTEN, TIMP3 (tissue inhibitor of metalloproteinase 3) (both inhibitors of the matrix metalloproteinases), BCL-2 (regulator of apoptosis) [ 208 ], and many others; its overexpression is linked to loss of function of TP53, which is most commonly observed in high-grade MIBC [ 209 ].…”

MicroRNAs as Urinary Biomarker for Oncocytoma

“…Most noteworthy for our purpose of specificity as an oncocytoma marker, miR-205 is downregulated in prostate cancers [ 54 ]. Furthermore, most publications (except [ 55 , 56 ]) also report a downregulation in bladder cancer, including a review of 108 relevant publications [ 57 , 58 ]. In addition, a study focusing on miR levels in biofluids (serum, urine) has found that miR-205 was so low that it can no longer be considered a useful biomarker [ 59 ].…”

<p>The functions of microRNA-124 on bladder cancer</p>

“…For example, abnormal expression of miRNA in BC is thought to benefit for the development of BC 10,11. Studies find that miRNA can be used as a marker for diagnosing BC and prognosis 12–14. MicroRNA-124 is considered to be brain-enriched and is an extremely conserved gene 15.…”