TY - JOUR
T1 - The lncRNA CASC15 regulates SOX4 expression in RUNX1-rearranged acute leukemia
AU - Fernando, Thilini R.
AU - Contreras, Jorge R.
AU - Zampini, Matteo
AU - Rodriguez-Malave, Norma I.
AU - Alberti, Michael O.
AU - Anguiano, Jaime
AU - Tran, Tiffany M.
AU - Palanichamy, Jayanth K.
AU - Gajeton, Jasmine
AU - Ung, Nolan M.
AU - Aros, Cody J.
AU - Waters, Ella V.
AU - Casero, David
AU - Basso, Giuseppe
AU - Pigazzi, Martina
AU - Rao, Dinesh S.
PY - 2017/7/19
Y1 - 2017/7/19
N2 - Background: Long non-coding RNAs (lncRNAs) play a variety of cellular roles, including regulation of transcription and translation, leading to alterations in gene expression. Some lncRNAs modulate the expression of chromosomally adjacent genes. Here, we assess the roles of the lncRNA CASC15 in regulation of a chromosomally nearby gene, SOX4, and its function in RUNX1/AML translocated leukemia. Results: CASC15 is a conserved lncRNA that was upregulated in pediatric B-acute lymphoblastic leukemia (B-ALL) with t (12; 21) as well as pediatric acute myeloid leukemia (AML) with t (8; 21), both of which are associated with relatively better prognosis. Enforced expression of CASC15 led to a myeloid bias in development, and overall, decreased engraftment and colony formation. At the cellular level, CASC15 regulated cellular survival, proliferation, and the expression of its chromosomally adjacent gene, SOX4. Differentially regulated genes following CASC15 knockdown were enriched for predicted transcriptional targets of the Yin and Yang-1 (YY1) transcription factor. Interestingly, we found that CASC15 enhances YY1-mediated regulation of the SOX4 promoter. Conclusions: Our findings represent the first characterization of this CASC15 in RUNX1-translocated leukemia, and point towards a mechanistic basis for its action.
AB - Background: Long non-coding RNAs (lncRNAs) play a variety of cellular roles, including regulation of transcription and translation, leading to alterations in gene expression. Some lncRNAs modulate the expression of chromosomally adjacent genes. Here, we assess the roles of the lncRNA CASC15 in regulation of a chromosomally nearby gene, SOX4, and its function in RUNX1/AML translocated leukemia. Results: CASC15 is a conserved lncRNA that was upregulated in pediatric B-acute lymphoblastic leukemia (B-ALL) with t (12; 21) as well as pediatric acute myeloid leukemia (AML) with t (8; 21), both of which are associated with relatively better prognosis. Enforced expression of CASC15 led to a myeloid bias in development, and overall, decreased engraftment and colony formation. At the cellular level, CASC15 regulated cellular survival, proliferation, and the expression of its chromosomally adjacent gene, SOX4. Differentially regulated genes following CASC15 knockdown were enriched for predicted transcriptional targets of the Yin and Yang-1 (YY1) transcription factor. Interestingly, we found that CASC15 enhances YY1-mediated regulation of the SOX4 promoter. Conclusions: Our findings represent the first characterization of this CASC15 in RUNX1-translocated leukemia, and point towards a mechanistic basis for its action.
KW - B-all
KW - CASC15
KW - ETV6-RUNX1
KW - Non-coding RNA
KW - SOX4
UR - http://www.scopus.com/inward/record.url?scp=85025083914&partnerID=8YFLogxK
U2 - 10.1186/s12943-017-0692-x
DO - 10.1186/s12943-017-0692-x
M3 - Article
C2 - 28724437
AN - SCOPUS:85025083914
VL - 16
JO - Molecular Cancer
JF - Molecular Cancer
SN - 1476-4598
IS - 1
M1 - 126
ER -