Austin Virol and Retrovirology. 2016; 3(1): 1017.
School of Biotechnology, KIIT University, India
*Corresponding author: Niladri Ganguly, School of Biotechnology, KIIT University, Bhubaneswar 751024, India
Received: January 30, 2016; Accepted: February 08, 2016; Published: February 09, 2016
Cervical cancer is the third most common cancer among women after breast and ovarian cancers. Almost 99% of cervical cancer samples contain Human Papillomavirus (HPV) DNA . HPV is a non enveloped virus containing circular double stranded DNA as its genome. There are more than 100 types of HPV that have been identified till date. HPVs are classified into high risk types (HPV16, HPV18, and HPV31) or low risk types (HPV6, HPV11) depending on their ability to cause malignant tumor or benign warts/lesions respectively.
Micro RNAs (miR) are short single stranded RNA molecules of 20-24 nucleotides in length that are important molecules involved in epigenetic regulation of gene expression . The inhibition of gene expression can be through transcriptional repression as well inhibition of translation by degradation of the corresponding messenger RNA. The genes encoding the miRs are found in the introns and intergenic sequences. Studies from different types of cancer samples using microarray expression analysis have clearly pointed to the role of miRs in cancer [3-6]. Mouse models having miRs overexpressed or ablated demonstrated the critical link between miRs and cancer progression.
Since the discovery about the roles of miRs in influencing cancer phenotype, several studies have been done on the miRs that are aberrantly expressed in cervical cancer cells. The analysis of the expression profile analysis was reviewed recently by Sharma et al. . The expression of miRs vary between different stages of Cervical Intraepithelial Neoplasia (CIN) i.e. CIN1, 2 and 3. Most miRs show a consistent up regulation or down regulation throughout the different CIN stages e.g. miR181, 191, 429, 214, 218, 143, 145, 497 etc. However, some miRs show an opposite trend while progressing from low grade (CIN1) to high grade (CIN3) cervical cancer e.g. miR 212, 132, 100 etc. The up regulation or down regulation of the respective miRs might be the cause of transition of the cancer from low to high grade. Thus miRs might be a useful marker for different stages of cervical cancer and to indicate the progression through different stages. Circulating miRs like miR-20a is one such biomarker for cervical cancer to found in lymph node .
Since miRs control the expression of several genes, studies have identified the cellular target genes that are affected by specific miRs. Some miRs like miR-214 have five validated cellular targets while others like miR-205, miR-34a and miR-133b have three validated cellular targets. The table below shows the miRs along with their respective validated cellular target genes in cervical cancer.
Validated cellular target genes
HOX , CHL1 
PDCD4 [14,15], CCL20 
Urokinase type Plasminogen Activator (uPA) 
YY1, CDK6 
Notch 1, Jagged 1 , p18Ink4c 
MST2, CDC42 , RHOA 
SMAD2, CCND1 
SHIP2 , CYR61, CTGF 
MEK3, JNK1, plexinB1, GALNT7, Bcl2l2 [30-33]
CDK2, CYCLINA1 
There are about 246 miRNAs in cervical cancer that are deregulated and the cellular targets for these miRNAs have been experimentally validated. These deregulated miRNAs affect a host of cellular processes like apoptosis, cell cycle regulation, metastasis, angiogenesis etc. The complex interplay of hundreds of miRNAs ensures the development of cancerous phenotype and ultimately progression from CIN1 to CIN3 stage.
The miRNA mediated gene regulation is fast becoming a hot topic for cervical cancer research. Their ability to post transcriptionally affect diverse cellular pathways makes them good candidates for targeting in cancer therapy. MiRNAs are also being studied for their ability to act as biomarkers for different stages of cervical cancer. Expression profile analysis for miRNAs from a patient sample can give a lot of information about the disease prognosis. More studies will reveal the detailed mechanisms by which the miRNAs gets deregulated in cervical cancer. It is important to determine the suitable miRNAs for therapeutic purpose.
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