Three Prime Repair Exonuclease 1 (TREX1) expression correlates with cervical cancer cells growth in vitro and disease progression in vivo

Autor(es):Mostrar menos -

Prati, Bruna ^[1] ; Abjaude, Walason da Silva ^[1] ; Termini, Lara ^[2] ; Morale, Mirian ^[3] ; Herbster, Suellen ^[1] ; Longatto-Filho, Adhemar ^{[4, 5, 6]} ; Lima Nunes, Rafaella Almeida ^[2] ; Cordoba Camacho, Lizeth Carolina ^{[1, 7, 8]} ; Rabelo-Santos, Silvia Helena ^[9] ; Zeferino, Luiz Carlos ^[10] ; Aguayo, Francisco ^{[11, 12]} ; Boccardo, Enrique ^[1]

Afiliação do(s) autor(es):Mostrar menos -

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Ave Prof Lineu Prestes 1374, BR-05508900 Sao Paulo, SP - Brazil

^[2] Inst Canc Estado Sao Paulo, Ctr Invest Translac Oncol LIM24, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sch Med, Dept Pathol, Lab Med Invest LIM 14, Ave Dr Arnaldo 455, BR-01246903 Sao Paulo - Brazil

^[5] Univ Minho, ICVS 3Bs PT Govt Associate Lab, Sch Hlth Sci, Life & Hlth Sci Res Inst, Braga, Guimaraes - Portugal

^[6] Barretos Canc Hosp, Pio XII Fdn, Mol Oncol Res Ctr, Rua Antenor Duarte Villela 1331, BR-14784400 Barretos - Brazil

^[7] Univ Sao Paulo, Fac Med, Lab Oncol Expt, Dept Radiol, Sao Paulo, SP - Brazil

^[8] ICESP, Ctr Invest Translac Oncol, Sao Paulo, SP - Brazil

^[9] Univ Fed Goias, Sch Pharm, Ave Univ, BR-74605220 Goiania, Go - Brazil

^[10] State Univ Campinas UNICAMP, Sch Med Sci, Rua Alexander Fleming 101, BR-13083881 Campinas, SP - Brazil

^[11] Univ Chile, Basic & Clin Oncol Dept, Fac Med, Santiago - Chile

^[12] Pontificia Univ Catolica Chile, Adv Ctr Chron Dis ACCDiS, Santiago - Chile

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 9, JAN 23 2019.
• Citações Web of Science: 0

Resumo

Alterations in specific DNA damage repair mechanisms in the presence of human papillomavirus (HPV) infection have been described in different experimental models. However, the global effect of HPV on the expression of genes involved in these pathways has not been analyzed in detail. In the present study, we compared the expression profile of 135 genes involved in DNA damage repair among primary human keratinocytes (PHK), HPV-positive (SiHa and HeLa) and HPV-negative (C33A) cervical cancer derived cell lines. We identified 9 genes which expression pattern distinguishes HPV-positive tumor cell lines from C33A. Moreover, we observed that Three Prime Repair Exonuclease 1 (TREX1) expression is upregulated exclusively in HPV-transformed cell lines and PHK expressing HPV16 E6 and E7 oncogenes. We demonstrated that TREX1 silencing greatly affects tumor cells clonogenic and anchorage independent growth potential. We showed that this effect is associated with p53 upregulation, accumulation of subG1 cells, and requires the expression of E7 from high-risk HPV types. Finally, we observed an increase in TREX1 levels in precancerous lesions, squamous carcinomas and adenocarcinomas clinical samples. Altogether, our results indicate that TREX1 upregulation is important for cervical tumor cells growth and may contribute with tumor establishment and progression. (AU)

• Processo FAPESP: 08/57889-1 - Instituto de Ciência e Tecnologia para o Estudo das Doenças Associadas ao Papilomavírus
• Beneficiário: Luisa Lina Villa
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 10/20002-0 - Estudo de Letalidade Sintética em células infectadas por papilomavírus humano (HPV)
• Beneficiário: Enrique Mario Boccardo Pierulivo
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 13/27006-9 - Estudo do papel da proteína reck no processo de carcinogênese mediado pelo papilomavírus humano
• Beneficiário: Suellen da Silva Gomes Herbster
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 12/16512-8 - Estudo de Letalidade Sintética em células transformadas por papilomavírus humano (HPV)
• Beneficiário: Walason da Silva Abjaude
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 11/14416-9 - Estudo dos Efeitos de E6 e E7 de HPV16 e HPV6 nas vias de sinalização iniciadas por Toll like receptors (TLR)
• Beneficiário: Mirian Galliote Morale
• Modalidade de apoio: Bolsas no Brasil - Doutorado