TY - JOUR
T1 - Aberrant expression of long non coding RNA HOTAIR and De-regulation of the paralogous 13 HOX genes are strongly associated with aggressive behavior of gastro-entero-pancreatic neuroendocrine tumors
AU - Di Mauro, Annabella
AU - Scognamiglio, Giosuè
AU - Aquino, Gabriella
AU - Cerrone, Margherita
AU - Liguori, Giuseppina
AU - Clemente, Ottavia
AU - Di Bonito, Maurizio
AU - Cantile, Monica
AU - Botti, Gerardo
AU - Tafuto, Salvatore
AU - Tatangelo, Fabiana
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/7/1
Y1 - 2021/7/1
N2 - Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) are rare diseases oc-curring in the gastrointestinal tract and pancreas. They are characterized by the loss of epithelial tubular gland elements, and by the increased expression of neuroendocrine markers. GEP-NENs are subdivided into two histo-pathological types, gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) and gastro-entero-pancreatic neuroendocrine carcinomas (GEP-NECs). According to WHO 2017 and 2019 classification criteria are graded and staged in four categories, NET-G1, NET-G2, NET-G3, and NEC-G3. The molecular characterization of these tumors can be fundamental for the identification of new diagnostic, prognostic and predictive biomarkers. The main purpose of this study was to analyze the expression of the paralogous 13 HOX genes, normally involved in embryogenic development and frequently deregulated in human cancers, and of the HOX regulating lncRNA HOTAIR in GEP-NENs. The expression of HOX genes is gradually lost in the transition from GEP NET G1 to NET/NEC G3 tumors, while HOTAIR expression, inversely correlated with HOX genes expression and weakly expressed in low-grade GEP NENs, becomes aberrant in NET G3 and NEC G3 categories. Our data highlights their potential role in the molecular stratification of GEP-NENs by suggesting new prognostic markers and potential therapeutic targets.
AB - Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) are rare diseases oc-curring in the gastrointestinal tract and pancreas. They are characterized by the loss of epithelial tubular gland elements, and by the increased expression of neuroendocrine markers. GEP-NENs are subdivided into two histo-pathological types, gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) and gastro-entero-pancreatic neuroendocrine carcinomas (GEP-NECs). According to WHO 2017 and 2019 classification criteria are graded and staged in four categories, NET-G1, NET-G2, NET-G3, and NEC-G3. The molecular characterization of these tumors can be fundamental for the identification of new diagnostic, prognostic and predictive biomarkers. The main purpose of this study was to analyze the expression of the paralogous 13 HOX genes, normally involved in embryogenic development and frequently deregulated in human cancers, and of the HOX regulating lncRNA HOTAIR in GEP-NENs. The expression of HOX genes is gradually lost in the transition from GEP NET G1 to NET/NEC G3 tumors, while HOTAIR expression, inversely correlated with HOX genes expression and weakly expressed in low-grade GEP NENs, becomes aberrant in NET G3 and NEC G3 categories. Our data highlights their potential role in the molecular stratification of GEP-NENs by suggesting new prognostic markers and potential therapeutic targets.
KW - GEP-NENs
KW - HOX genes
KW - LncRNA HOTAIR
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U2 - 10.3390/ijms22137049
DO - 10.3390/ijms22137049
M3 - Article
AN - SCOPUS:85108881806
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 13
M1 - 7049
ER -