Serum one-carbon metabolites and risk of cervical cancer.
Most cases of cervical cancer are associated with human papilloma virus (HPV) infection of high risk types. In folate deficiency, heterogeneous nuclear ribonucleoprotein E1 (hnRNP-E1) interferes with HPV16 viral capsid protein synthesis. We aimed to study the importance of 1-carbon metabolism in cervical carcinogenesis by examining serum vitamin B12 (cobalamin), homocysteine, folate levels, and the RNA and protein expression of HPV16 L1, L2, E6, E7, and to correlate them with hnRNP-E1 expression and HPV infection in normals, squamous intraepithelial lesions (SILs), and cervical cancer subjects. Serum cobalamin, folate, and homocysteine were estimated using kits, RNA by real time PCR and proteins by Western blotting. We observed that lower folate and vitamin B12 levels were associated with HPV infection. hnRNP-E1 progressively decreased from normals (100%) to SILs (75%) to cervical cancer (52.6%). The findings show that HPV16 E6 and E7 are overexpresed whereas HPV16 L1 and L2 are downregulated at mRNA and protein levels in cervical cancer as compared to normals and SILs. The results indicate that perhaps the reduced expression of hnRNP-E1 might be involved with the cervical cancer pathogenesis, with folate playing a role in the natural history of HPV infection.
a Department of Biochemistry , All India Institute of Medical Sciences , New Delhi , India.
Sujata
S
Pathak
Deepti
D
Bajpai
Ayan
A
Banerjee
Neerja
N
Bhatla
Sunesh Kumar
SK
Jain
Hiremagular N
HN
Jayaram
Neeta
N
Singh
D000328:Adult; D000368:Aged; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D005260:Female; D005492:Folic Acid / Q000097:blood*; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D030361:Papillomavirus Infections / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D012097:Repressor Proteins / Q000378:metabolism; D012307:Risk Factors; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000097:blood / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000097:blood* / Q000473:pathology / Q000821:virology; D014764:Viral Proteins / Q000378:metabolism; D014805:Vitamin B 12 / Q000097:blood*
D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009856:Oncogene Proteins, Viral; C094604:PCBP1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014764:Viral Proteins; D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12