Expression analysis of ST 3 GAL 4 transcripts in cervical cancer cells

ST3GAL4 gene expression is altered in different cancer types, including cervical cancer. Several mRNA transcripts have been reported for this gene; however, their expression levels in cervical cancer have not been analyzed. ST3GAL4 encodes for β-galactosidase α-2,3-sialyltransferase 4, involved in the biosynthesis of the tumour antigens sLe(x) and sulfo-sLe(x). The present study evaluated the presence of three mRNA variants (V1, V2 and V3) in cervical cancer cell lines, detecting the three variants. Additionally, the expression level of the V1 transcript of the ST3GAL4 gene was determined by reverse transcription-quantitative polymerase chain reaction in cervical cell lines and in normal, premalignant and cervical cancer tissue. The V1 transcript of the ST3GAL4 demonstrated significant decreased expression in premalignant and malignant cervical tissues. The results suggested that deregulation of this gene could occur prior to the presence of cancer and demonstrated the importance of evaluating the expression level of V1, and its association with disease progression. Introduction The ST3GA L 4 gene encodes for β -ga lactoside α-2,3-sialyltransferase 4 (ST3Gal IV), enzyme that transfers sialic acid to the type 2 precursor (Galβ1,4GlcNAc). It is involved in the biosynthesis of the sLe(x) and sulfo-sLe(x) epitopes (1-3). Alteration of sialyltransferase gene expression has been implicated in carcinogenesis. Specifically, expression of this gene is altered in different cancer types. ST3GAL4 expression is decreased in renal cell carcinoma and cervical cancer (4,5), whereas it is increased in gastric cancer and in premalignant lesions of the cervix (6,7). For other cancer types, including colorectal cancer, the expression level of ST3GAL4 does not demonstrate any changes (8). Sialyltransferase genes are regulated in a tissue specific manner; that is, gene expression may be regulated by different promoters, and their alternative use can regulate gene expression in different tissues. Thus far, five different promoters have been reported for the ST3GAL4 gene: pA, pB1, pB2, pB3 and pBx (9,10). Complexity of the gene expression increases since six mRNA isoforms have also been reported: A1, A2, B1, B2, B3 and B4 (1,11,12) and these may be produced by combinations of promoter utilization and alternative splicing. The transcript isoforms (9,10) are now listed in GenBank (https://www.ncbi.nlm.nih.gov/genbank/) as variant transcripts. The expression of these variants has not been evaluated in cervical cancer cells. To better understand the mechanisms by which the expression of the ST3GAL4 gene is regulated in cervical cancer, it is important to determine the transcript variants present in this tissue and how their expression is modified during tumour transformation. Expression analysis of ST3GAL4 transcripts in cervical cancer cells LORENA ROA-DE LA CRUZ1, PATRICIA MARTÍNEZ-MORALES2, IRENE MORÁN-CRUZ1, LORENA MILFLORES-FLORES3, NORA ROSAS-MURRIETA4, CÉSAR GONZÁLEZ-RAMÍREZ5, CLAUDIA ORTIZ-MATEOS1,3, RICARDO MONTERROSAS-SANTAMARÍA1, CELESTINA GONZÁLEZ-FRÍAS6, CARLOS RODEA-ÁVILA7, TERESA APRESA-GARCÍA7, ADRIANA AGUILAR-LEMARROY8, LUIS JAVE-SUAREZ8, GERARDO SANTOS-LÓPEZ1, JULIO REYES-LEYVA1 and VERÓNICA VALLEJO-RUIZ1 1Instituto Mexicano del Seguro Social, Centro de Investigación Biomédica de Oriente, Laboratorio de Biología Molecular, C.P. Metepec, Puebla 74360; 2CONACYTCentro de Investigación Biomédica de Oriente (CIBIOR), Metepec, Puebla 74360; 3Escuela de Biología, Benemérita Universidad Autónoma de Puebla, Puebla, Puebla 72570; 4Laboratorio de Bioquímica y Biología Molecular, Instituto de Ciencias Benemérita Universidad Autónoma de Puebla, Puebla, Puebla 72570; 5Instituto Mexicano del Seguro Social, Hospital General de Zona No. 15, Tehuacán, Puebla 75710; 6Instituto Mexicano del Seguro Social, Hospital General Regional No. 36, Puebla, Puebla 72090; 7Instituto Mexicano del Seguro Social, Centro Médico Nacional sXXI, Mexico City 06720; 8Instituto Mexicano del Seguro Social, Centro de Investigación Biomédica de Occidente, Guadalajara, Jalisco 44340, Mexico Received May 17, 2017; Accepted March 1, 2018 DOI: 10.3892/mmr.2018. 8938 Correspondence to: Dr Verónica Vallejo-Ruiz, Instituto Mexicano del Seguro Social, Centro de Investigación Biomédica de Oriente, Laboratorio de Biología Molecular, Km 4.5 Carretera Federal, Atlixco-Metepec, C.P. Metepec, Puebla 74360, México E-mail: veronica.vallejor@imss.gob. mx