TY - JOUR
T1 - circPVT1 and PVT1/AKT3 show a role in cell proliferation, apoptosis, and tumor subtype-definition in Small Cell Lung Cancer
AU - Tolomeo, Doron
AU - Traversa, Debora
AU - Venuto, Santina
AU - Ebbesen, Karoline
AU - Garcia Rodriguez, Juan Luis
AU - Tamma, Grazia
AU - Ranieri, Marianna
AU - Simonetti, Giorgia
AU - Ghetti, Martina
AU - Paganelli, Matteo
AU - Visci, Grazia
AU - Liso, Arcangelo
AU - Kok, Klaas
AU - Muscarella, Lucia Anna
AU - Fabrizio, Federico Pio
AU - Frassanito, Maria Antonia
AU - Lamanuzzi, Aurelia
AU - Saltarella, Ilaria
AU - Solimando, Antonio Giovanni
AU - Fatica, Alessandro
AU - Ianiello, Zaira
AU - Marsano, René Massimiliano
AU - Palazzo, Antonio
AU - Azzariti, Amalia
AU - Longo, Vito
AU - Tommasi, Stefania
AU - Galetta, Domenico
AU - Catino, Annamaria
AU - ZIto, Alfredo
AU - Mazza, Tommaso
AU - Napoli, Alessandro
AU - Martinelli, G
AU - Kjems, Jørgen
AU - Kristensen, Lasse Sommer
AU - Vacca, Angelo
AU - Storlazzi, Clelia Tiziana
PY - 2023/7
Y1 - 2023/7
N2 - Small Cell Lung Cancer (SCLC) is treated as a homogeneous disease, although the expression of NEUROD1, ASCL1, POU2F3, and YAP1 identifies distinct molecular subtypes. The MYC oncogene, amplified in SCLC, was recently shown to act as a lineage-specific factor to associate subtypes with histological classes. Indeed, MYC-driven SCLCs show a distinct metabolic profile and drug sensitivity. To disentangle their molecular features, we focused on the co-amplified PVT1, frequently overexpressed and originating circular (circRNA) and chimeric RNAs. We analyzed hsa_circ_0001821 (circPVT1) and PVT1/AKT3 (chimPVT1) as examples of such transcripts, respectively, to unveil their tumorigenic contribution to SCLC. In detail, circPVT1 activated a pro-proliferative and anti-apoptotic program when over-expressed in lung cells, and knockdown of chimPVT1 induced a decrease in cell growth and an increase of apoptosis in SCLC in vitro. Moreover, the investigated PVT1 transcripts underlined a functional connection between MYC and YAP1/POU2F3, suggesting that they contribute to the transcriptional landscape associated with MYC amplification. In conclusion, we have uncovered a functional role of circular and chimeric PVT1 transcripts in SCLC; these entities may prove useful as novel biomarkers in MYC-amplified tumors.
AB - Small Cell Lung Cancer (SCLC) is treated as a homogeneous disease, although the expression of NEUROD1, ASCL1, POU2F3, and YAP1 identifies distinct molecular subtypes. The MYC oncogene, amplified in SCLC, was recently shown to act as a lineage-specific factor to associate subtypes with histological classes. Indeed, MYC-driven SCLCs show a distinct metabolic profile and drug sensitivity. To disentangle their molecular features, we focused on the co-amplified PVT1, frequently overexpressed and originating circular (circRNA) and chimeric RNAs. We analyzed hsa_circ_0001821 (circPVT1) and PVT1/AKT3 (chimPVT1) as examples of such transcripts, respectively, to unveil their tumorigenic contribution to SCLC. In detail, circPVT1 activated a pro-proliferative and anti-apoptotic program when over-expressed in lung cells, and knockdown of chimPVT1 induced a decrease in cell growth and an increase of apoptosis in SCLC in vitro. Moreover, the investigated PVT1 transcripts underlined a functional connection between MYC and YAP1/POU2F3, suggesting that they contribute to the transcriptional landscape associated with MYC amplification. In conclusion, we have uncovered a functional role of circular and chimeric PVT1 transcripts in SCLC; these entities may prove useful as novel biomarkers in MYC-amplified tumors.
KW - MYC
KW - PVT1
KW - circular RNA
KW - fusion transcript
KW - small cell lung cancer
KW - Humans
KW - Gene Expression Regulation, Neoplastic
KW - Small Cell Lung Carcinoma/genetics
KW - Apoptosis/genetics
KW - Proto-Oncogene Proteins c-akt/genetics
KW - Lung Neoplasms/genetics
KW - Cell Line, Tumor
KW - Cell Proliferation/genetics
U2 - 10.1002/gcc.23121
DO - 10.1002/gcc.23121
M3 - Journal article
C2 - 36562080
SN - 1045-2257
VL - 62
SP - 377
EP - 391
JO - Genes, Chromosomes & Cancer
JF - Genes, Chromosomes & Cancer
IS - 7
ER -