SNP rs1049430 in the 3'-UTR of SH3GL2 regulates its expression: Clinical and prognostic implications in head and neck squamous cell carcinoma.
Single nucleotide polymorphisms (SNPs) in the 3'-UTR region are emerging cis-regulatory factors associated with the occurrences of several human diseases. SH3GL2, which is located at chromosome 9p21-22, is associated with hyperplastic/mildly dysplastic lesions of the head and neck and has a long 3'-UTR with multiple SNPs. The aim of the present study was to determine the susceptible allele(s) in the 3'-UTR SNPs of SH3GL2 in head and neck squamous cell carcinoma (HNSCC). First, we screened the genotypes of all SNPs located in the 3'-UTR of SH3GL2 in 110 controls and 147 cases in Indian populations by sequencing. A SNP (rs1049430:>G/T) that showed only heterozygosity was further confirmed by genotyping with an Illumina GoldenGate platform in 530 controls and 764 cases. Genotype-specific survival analysis of the HNSCC patients was performed. In addition, genotype-specific mRNA stability, isoform expression and protein expression were analyzed. SNP rs1049430 was not associated with disease occurrence, but it was associated with poor patient outcome. The G allele was associated with decreased SH3GL2 mRNA stability, differential splicing and low protein expression. Thus, our data demonstrate that the presence of the susceptible G allele in SNP rs1049430 is associated with the inactivation of SH3GL2 and could be used as a prognostic marker of HNSCC.
Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, India; Department of Molecular Biology and Biotechnology, University of Kalyani, Kalyani, Nadia, WB, India.
Guru Prasad
GP
Maiti
Department of Biological Science, Presidency University, Kolkata, India.
Amlan
A
Ghosh
National Brain Research Centre, NH-8, Manesar, Gurgaon, Haryana 122051, India.
Pinaki
P
Mondal
Proteomics and Structural Biology Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.
Aradhita
A
Baral
Human Genetics Unit, Indian Statistical Institute, Kolkata, West Bengal, India; Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Sayantan
S
Datta
Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, India.
Sudip
S
Samadder
Department of Surgical Oncology, Kidwai Memorial Institute of Oncology, Marigowda Road, Bangalore 560029, India.
Sandeep P
SP
Nayak
Department of Surgical Oncology, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, India.
Jayanta
J
Chakrabarti
Department of Surgical Oncology, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, India.
Jaydeep
J
Biswas
Human Genetics Unit, Indian Statistical Institute, Kolkata, West Bengal, India.
Nilabja
N
Sikdar
Proteomics and Structural Biology Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.
Shantanu
S
Chowdhury
Human Genetics Unit, Indian Statistical Institute, Kolkata, West Bengal, India.
Bidyut
B
Roy
Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India.
Susanta
S
Roychowdhury
Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, India. Electronic address: ckpanda.cnci@gmail.com.
Chinmay Kumar
CK
Panda
D020413:3' Untranslated Regions / Q000235:genetics*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D061986:MCF-7 Cells; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D020871:RNA Stability / Q000235:genetics; D055815:Young Adult; D018909:src Homology Domains / Q000235:genetics
D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; C107640:SH3GL2 protein, human
3′-UTR; Allele-specific isoform; HNSCC; SH3GL2; rs1049430