Micro Rnas in Human Papillomavirus Mediated Cervical Cancer

Editorial

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 [1]. 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 [2]. 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.

Abstract

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. [7]. 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 [8].

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.

  

    
Micro    RNA 
    
Validated    cellular target genes 
  
  

    
miR10a 
    
HOX    [9], CHL1 [10] 
  
  

    
miR17 
    
TP53INP1    [11] 
  
  

    
miR19a,    miR19b 
    
CUL5    [12] 
  
  

    
miR20a 
    
TNKS2    [13] 
  
  

    
miR21 
    
PDCD4    [14,15], CCL20 [16] 
  
  

    
miR23b 
    
Urokinase    type Plasminogen Activator (uPA) [17] 
  
  

    
miR29a 
    
YY1,    CDK6 [18] 
  
  

    
miR34a 
    
Notch    1, Jagged 1 [19], p18Ink4c [20] 
  
  

    
miR100 
    
PLK1    [21] 
  
  

    
miR125b 
    
PIK3CD    [22] 
  
  

    
miR133b 
    
MST2,    CDC42 , RHOA [23] 
  
  

    
miR143 
    
Bcl2    [24] 
  
  

    
miR145 
    
IRS1    [25] 
  
  

    
miR155 
    
SMAD2,    CCND1 [26] 
  
  

    
miR182 
    
FOXO1    [27] 
  
  

    
miR196a 
    
HOX    [9] 
  
  

    
miR205 
    
SHIP2    [28], CYR61, CTGF [29] 
  
  

    
miR    214 
    
MEK3,    JNK1, plexinB1, GALNT7, Bcl2l2 [30-33] 
  
  

    
miR218 
    
LAMB3    [34-36] 
  
  

    
miR223 
    
FOXO1    [37] 
  
  

    
miR302-367 
    
CYCLIND1    [38] 
  
  

    
miR372 
    
CDK2,    CYCLINA1 [39] 
  
  

    
miR375 
    
SP1    [40] 
  
  

    
miR424 
    
Chk1    [41] 
  
  

    
miR497 
    
IGF-1R    [42] 
  
  

    
miR886-5p 
    
Bax    [43] 
  

Table 1: