MicroRNAs as Biomarkers in Cancer: (scientist)

Author: Eunice Lozada-Delgado

Recently, due to the advancements in sequencing and transcriptomics techniques, there have been many studies trying to identify gene biomarkers that can serve as therapeutic targets for different diseases like cancer. Now, other specific areas that are being studied with this goal is by using the non-coding region of the DNA. Specifically, recently there has been great interest in studying micro-RNAs as possible biomarkers. Here we will focus on the study of microRNAs as biomarkers in cancers.

Micro-RNAs (miRNAs) are small non-coding RNAs that are known to target and regulate gene expression at the mRNA level by targeting the 3’UTR of the mature mRNA molecule (Li et al., 2012). Further, in vitro and in vivo experiments have suggested that miRNAs can be used to target and regulate the expression of genes that are known drivers of tumorigenesis. MiRNAs have been associated with different biological roles like apoptosis, cell cycle, cell division, among others that are related to cancer progression (Pink et al., 2015). Thus, ideally one can develop different personalized therapeutic strategies towards patients with specific deregulated miRNAs.

miRNA biogenesis  

http://www.sigmaaldrich.com/life-science/functional-genomics-and-rnai/mirna/learning-center/mirna-introduction.html

As an example, a recent publication by Rivera-Diaz, et al. made a miRNA profile comparing differentially expressed miRNAs between WHO grades II-IV of astrocytoma patients (Rivera-Díaz et al., 2015). Here they used formalin-fixed patient samples in paraffin and compared the miRNA expression patterns between the different WHO grade patient tumor samples with both non-neoplastic surrounding tissue and control patients. They extracted the miRNA containing RNA from the different samples and conducted a microarray assay to obtain their results. They were able to obtain differentially expressed miRNA profiles distinguishing the various WHO grades. Afterwards, they validated one of the miRNAs found to be differentially expressed in astrocytoma grade IV, better known as Glioblastoma multiforme (GBM), miR-27a. When inhibiting this miRNA in CRL-1690 GBM cells an increase in apoptosis was obtained. Additionally, six potential targets for this miRNA were identified. The results obtained are of importance because GBM has a very high death rate in the United States. Moreover, the profiles obtained can now be used as biomarkers for the different stages or grades of astrocytoma tumors.

Left frontal GBM

http://www.uiowa.edu/~c064s01/nr094.htm

Another recent publication in the area is by Pink, et al. focusing on miRNA patterns of ovarian cancer cell lines resistant to cisplatin therapy (Pink et al., 2015). Here they made microarray analysis in cisplatin sensitive A2780 ovarian cancer cell line compared to the cisplatin resistant CP70 ovarian cancer cell line. Using this approach they were able to identify various miRNAs that were upregulated in the cisplatin resistant cells. Then they went and tested the role of some of these miRNAs with mimics, and of their targets with siRNAs. They identified miR-21-3p as having a role in cisplatin resistance, while it’s “sister strand” or star strand, miR-21-5p, had a contrary role by defining cisplatin sensitivity.  Afterwards, they identified a new target mRNA for the miR-21-3p, the NAV3 gene mRNA. Then to prove if this target had to do with the fact of miR-21-3p increasing cisplatin resistance they knocked down NAV3, and what resulted was an increase in cisplatin resistance. Thus suggesting that miR-21-3p increases cisplatin drug resistance through targeting of the NAV3 mRNA in ovarian cancer.  This study identifies miR-21-3p as a possible biomarker for ovarian cancer with cisplatin therapy resistance.

In summary, here we were able to demonstrate mainly through two recently published articles the interest in research to study microRNAs as biomarkers in different cancers. Here, two studies in different cancers were discussed, Glioblastoma multiforme and ovarian cancer, but the same type of study is being made in all types of cancer. This provides evidence of the emerging need to develop new types of therapies that can have personalized potential towards specific people within their type of cancer targeting their specific mutations.

Video on Profiling microRNA by pathway and disease: https://www.youtube.com/watch?=GsZpw5QEyKI

 

LI, Z.  et al. microRNA expression profiles in human colorectal cancers with brain metastases. Oncol Lett, v. 3, n. 2, p. 346-350, Feb 2012. ISSN 1792-1074. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/22740910 >.

PINK, R. C.  et al. The passenger strand, miR-21-3p, plays a role in mediating cisplatin resistance in ovarian cancer cells. Gynecol Oncol, Jan 2015. ISSN 1095-6859. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/25579119 >.

RIVERA-DÍAZ, M.  et al. MicroRNA-27a distinguishes glioblastoma multiforme from diffuse and anaplastic astrocytomas and has prognostic value. Am J Cancer Res, v. 5, n. 1, p. 201-18,  2015. ISSN 2156-6976. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/25628931 >.

itstimetoshout.com