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G Protein-coupled Receptor 91 (GPR91) Indicates Prognosis and Enhances Chemoresistance by Regulating DNA Damage Pathway and ERK Signaling Pathways in Neuroblastoma

ABSTRACT: This study first reveals that GPR91 is a potential oncogene in neuroblastoma, which is significantly correlated with poor prognosis and significantly represses the sensitivity to chemotherapeutic drugs including doxorubicin and cisplatin of NB cells. It is regulated by GPR91 though the DNA damage pathway and the ERK signaling pathway.

ORGANISM(S): Homo sapiens

PROVIDER: GSE199784 | GEO | 2022/04/02

REPOSITORIES: GEO

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Project description:Background:Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide, however, the mechanisms of CRC progression remain obscure. The present study investigated the clinical significance and functional role of long noncoding RNA (lncRNA) GIHCG in CRC. Methods:Expression of GIHCG was detected by quantitative real time polymerase chain reaction (qRT-PCR) in seven CRC cell lines and 110 CRC tissues. Comparison of clinicopathological characteristics in the high GIHCG expression group and the low GIHCG expression group was performed. The overall survival (OS) and progression-free survival (PFS) of the patients were depicted with Kaplan-Meier test and compared with Log-rank test. Univariate and multivariate analyses were carried out to detect the risk factors for poor OS and PFS. In addition, expression of GIHCG was silenced with siRNAs in LoVo cells and overexpressed with pcDNA3.1-GIHCG vector in SW480 cells, respectively. And the Transwell assay, Matrigel assay, colony formation assay and Cell Counting Kit-8 assay (CCK-8) were performed to investigate the role of GIHCG in the migration, invasion and proliferation of CRC cells. Besides, the role of GIHCG in chemoresistance was also detected. Results:GIHCG was overexpressed in seven CRC cell lines and 110 CRC tissues. High GIHCG expression was correlated with lymphovascular invasion, lymph node metastasis, distant metastasis and advanced TNM stages. Moreover, patients with high GIHCG expression had much poorer OS and PFS rates. Besides, high GIHCG expression was identified as an independent risk factor for poor OS and PFS. The Transwell assay and the Matrigel assay discovered that GIHCG deficiency inhibited cell migration and invasion, while ectopic expression of GIHCG promoted migration and invasion. Besides, the colony formation assay and the CCK-8 assay verified that GIHCG increased cell proliferation ability. By establishing 5-fluorouracil (5-FU) and Oxaliplatin (Oxa)-resistant LoVo cells and SW480 cells, we found chemoresistant CRC cells had much higher expression levels of GIHCG. Also, GIHCG facilitated cell survival under 5-FU or Oxa treatment. Furthermore, silencing of GIHCG notably reduced the improved cell survival rates of 5-FU or Oxa-resistant LoVo cells compared with control cells. Conclusion:GIHCG contributes to cancer progression and chemoresistance and indicates poor prognosis in CRC. GIHCG may be a promising prognostic biomarker and therapeutic target in CRC.

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G Protein-coupled Receptor 91 (GPR91) Indicates Prognosis and Enhances Chemoresistance by Regulating DNA Damage Pathway and ERK Signaling Pathways in Neuroblastoma

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