Dataset Information

PRKAR1B-AS2 Long Noncoding RNA Promotes Tumorigenesis, Survival, and Chemoresistance via the PI3K/AKT/mTOR Pathway.

ABSTRACT: Many long noncoding RNAs have been implicated in tumorigenesis and chemoresistance; however, the underlying mechanisms are not well understood. We investigated the role of PRKAR1B-AS2 long noncoding RNA in ovarian cancer (OC) and chemoresistance and identified potential downstream molecular circuitry underlying its action. Analysis of The Cancer Genome Atlas OC dataset, in vitro experiments, proteomic analysis, and a xenograft OC mouse model were implemented. Our findings indicated that overexpression of PRKAR1B-AS2 is negatively correlated with overall survival in OC patients. Furthermore, PRKAR1B-AS2 knockdown-attenuated proliferation, migration, and invasion of OC cells and ameliorated cisplatin and alpelisib resistance in vitro. In proteomic analysis, silencing PRKAR1B-AS2 markedly inhibited protein expression of PI3K-110? and abrogated the phosphorylation of PDK1, AKT, and mTOR, with no significant effect on PTEN. The RNA immunoprecipitation detected a physical interaction between PRKAR1B-AS2 and PI3K-110?. Moreover, PRKAR1B-AS2 knockdown by systemic administration of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine nanoparticles loaded with PRKAR1B-AS2-specific small interfering RNA enhanced cisplatin sensitivity in a xenograft OC mouse model. In conclusion, PRKAR1B-AS2 promotes tumor growth and confers chemoresistance by modulating the PI3K/AKT/mTOR pathway. Thus, targeting PRKAR1B-AS2 may represent a novel therapeutic approach for the treatment of OC patients.

SUBMITTER: Elsayed AM

PROVIDER: S-EPMC7918312 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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PRKAR1B-AS2 Long Noncoding RNA Promotes Tumorigenesis, Survival, and Chemoresistance via the PI3K/AKT/mTOR Pathway.

Elsayed Abdelrahman M AM Bayraktar Emine E Amero Paola P Salama Salama A SA Abdelaziz Abdelaziz H AH Ismail Raed S RS Zhang Xinna X Ivan Cristina C Sood Anil K AK Lopez-Berestein Gabriel G Rodriguez-Aguayo Cristian C

International journal of molecular sciences 20210213 4

Many long noncoding RNAs have been implicated in tumorigenesis and chemoresistance; however, the underlying mechanisms are not well understood. We investigated the role of PRKAR1B-AS2 long noncoding RNA in ovarian cancer (OC) and chemoresistance and identified potential downstream molecular circuitry underlying its action. Analysis of The Cancer Genome Atlas OC dataset, in vitro experiments, proteomic analysis, and a xenograft OC mouse model were implemented. Our findings indicated that overexpr ...[more]

PMID: 33668685

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Dataset Information

PRKAR1B-AS2 Long Noncoding RNA Promotes Tumorigenesis, Survival, and Chemoresistance via the PI3K/AKT/mTOR Pathway.

Publications

PRKAR1B-AS2 Long Noncoding RNA Promotes Tumorigenesis, Survival, and Chemoresistance via the PI3K/AKT/mTOR Pathway.

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