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Reciprocal interplay between asporin and decorin: Implications in gastric cancer prognosis.
Basak, Dipjit; Jamal, Zarqua; Ghosh, Arnab; Mondal, Pronoy Kanti; Dey Talukdar, Priyanka; Ghosh, Semanti; Ghosh Roy, Biswadeep; Ghosh, Ranajoy; Halder, Aniket; Chowdhury, Abhijit; Dhali, Gopal Krishna; Chattopadhyay, Bitan Kumar; Saha, Makhan Lal; Basu, Abhimanyu; Roy, Sukanta; Mukherjee, Chitranjan; Biswas, Nidhan Kumar; Chatterji, Urmi; Datta, Shalini.
Afiliação
  • Basak D; Human Genetics Unit, Indian Statistical Institute, Kolkata, India.
  • Jamal Z; Cancer Research Lab, Department of Zoology, University of Calcutta, Kolkata, India.
  • Ghosh A; National Institute of Biomedical Genomics, Kalyani, India.
  • Mondal PK; Human Genetics Unit, Indian Statistical Institute, Kolkata, India.
  • Dey Talukdar P; Cancer Research Lab, Department of Zoology, University of Calcutta, Kolkata, India.
  • Ghosh S; Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, Kolkata, India.
  • Ghosh Roy B; Human Genetics Unit, Indian Statistical Institute, Kolkata, India.
  • Ghosh R; The School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India.
  • Halder A; The School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India.
  • Chowdhury A; The School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India.
  • Dhali GK; The School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India.
  • Chattopadhyay BK; Department of Surgery, Institute of Post Graduate Medical Education and Research, Kolkata, India.
  • Saha ML; Department of Surgery, Institute of Post Graduate Medical Education and Research, Kolkata, India.
  • Basu A; Department of Surgery, Institute of Post Graduate Medical Education and Research, Kolkata, India.
  • Roy S; The School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India.
  • Mukherjee C; Delhi Technological University, Delhi, India.
  • Biswas NK; National Institute of Biomedical Genomics, Kalyani, India.
  • Chatterji U; Cancer Research Lab, Department of Zoology, University of Calcutta, Kolkata, India.
  • Datta S; Human Genetics Unit, Indian Statistical Institute, Kolkata, India.
PLoS One ; 16(8): e0255915, 2021.
Article em En | MEDLINE | ID: mdl-34379688
ABSTRACT
Effective patient prognosis necessitates identification of novel tumor promoting drivers of gastric cancer (GC) which contribute to worsened conditions by analysing TCGA-gastric adenocarcinoma dataset. Small leucine-rich proteoglycans, asporin (ASPN) and decorin (DCN), play overlapping roles in development and diseases; however, the mechanisms underlying their interplay remain elusive. Here, we investigated the complex interplay of asporin, decorin and their interaction with TGFß in GC tumor and corresponding normal tissues. The mRNA levels, protein expressions and cellular localizations of ASPN and DCN were analyzed using real-time PCR, western blot and immunohistochemistry, respectively. The protein-protein interaction was predicted by in-silico interaction analysis and validated by co-immunoprecipitation assay. The correlations between ASPN and EMT proteins, VEGF and collagen were achieved using western blot analysis. A significant increase in expression of ASPN in tumor tissue vs. normal tissue was observed in both TCGA and our patient cohort. DCN, an effective inhibitor of the TGFß pathway, was negatively correlated with stages of GC. Co-immunoprecipitation demonstrated that DCN binds with TGFß, in normal gastric epithelium, whereas in GC, ASPN preferentially binds TGFß. Possible activation of the canonical TGFß pathway by phosphorylation of SMAD2 in tumor tissues suggests its role as an intracellular tumor promoter. Furthermore, tissues expressing ASPN showed unregulated EMT signalling. Our study uncovers ASPN as a GC-promoting gene and DCN as tumor suppressor, suggesting that ASPN can act as a prognostic marker in GC. For the first time, we describe the physical interaction of TGFß with ASPN in GC and DCN with TGFß in GC and normal gastric epithelium respectively. This study suggests that prevention of ASPN-TGFß interaction or overexpression of DCN could serve as promising therapeutic strategies for GC patients.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Gástricas / Proteínas da Matriz Extracelular / Decorina Tipo de estudo: Prognostic_studies Limite: Female / Humans / Male / Middle aged Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Índia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Gástricas / Proteínas da Matriz Extracelular / Decorina Tipo de estudo: Prognostic_studies Limite: Female / Humans / Male / Middle aged Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Índia