ROBO1 protein expression is independently associated with biochemical recurrence in prostate cancer patients who underwent radical prostatectomy in Asian patients

Kim, Sang Hoon; Kim, Taejung; Shin, Dong–Ho; Hur, Kyung Jae; Hong, Sung-Hoo; Lee, Ji Youl; Ha, U-Syn

doi:10.21037/gs-21-406

Cited by 3 publications

(2 citation statements)

References 25 publications

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“…ROBO1 is highly expressed in the PCa cell lines. All ROBO1 knockdown cells (PC3, 22Rv1, and DU 145) showed markedly decreased migration and invasiveness compared to native cells [27]. LUZP2, a gene encoding leucine zipper protein 2, is located at 11p14.3 and is primarily expressed in the brain tissue and prostate, which was rarely studied in the field of oncology before, and its downregulation is associated with senescence [28].…”

Section: Discussionmentioning

confidence: 99%

Parkinson’s Disease as a Risk Factor for Prostate Adenocarcinoma: A Molecular Point of View

Liu¹,

Yang²,

Liu³

et al. 2023

Gerontology

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Introduction: Cancer and neurodegeneration are two major leading causes of morbidity and death worldwide. Neurodegeneration results in excessive neuronal cell death, and cancer emerges from increased proliferation and resistance to cell death. Although most epidemiological studies support an inverse association between the risk for the development of neurodegenerative diseases and cancer, increasing evidence points to a positive correlation between specific types of cancer, like prostate adenocarcinoma (PRAD), and neurodegenerative diseases, like Parkinson’s disease (PD). Methods: PD and PRAD differential genes were screened through the GEO database, and the differential genes were analyzed using David, String, GEPIA, Kaplan-Meier plotter, TIMER2.0, proteinatlas, cBioPortal, and CTD databases. To elucidate the biological function and molecular mechanism of PD and PRAD-related genes. Results: Studies have shown that the hub gene and differentially expressed genes (DEGs) in PD were differentially expressed in PRAD, including CDC20, HSPA4L, ROBO1, DMKN, IFI27L2, LUZP2, PTN, PTGDS. In PRAD, the high expression of HSPA4L, ROBO1, DMKN, IFI27L2, PTN, and PTGDS genes were associated with longer survival, while the patients with low expression of CDC20 and LUZP2 genes have longer survival. The mRNA of CDC20 and LUZP2 were highly expressed, while the mRNA of HSPA4L, ROBO1, DMKN, IFI27L2, and PTGDS were low expressed. Gene methylation did not affect the survival of patients. The high expression of miR-142, miR-186, miR-30a, miR-497, miR-590, miR-28, and miR-576 in micro RNA (miRNA) might potentially be used as biomarkers for the progression of PD and PRAD, and for the early diagnosis of PD and PRAD in the populations. The genes in this study were highly associated with B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Somatic mutation mainly focused on missense mutation. Therapeutic drugs included Acetaminophen and Valproic Acid (VPA). Conclusion: Bioinformatics was used to identify potential targets and novel molecular mechanisms that may serve as clinical markers for the diagnosis and treatment of PD and PRAD.

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Section: Discussionmentioning

confidence: 99%

Parkinson’s Disease as a Risk Factor for Prostate Adenocarcinoma: A Molecular Point of View

Liu¹,

Yang²,

Liu³

et al. 2023

Gerontology

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“…A comprehensive genomic study has identified Robo1 gene mutations in SCLC patients [ 29 ]. Genetic and immunological inhibition of Robo1 has established its oncogenic role in multiple myeloma and prostate cancer in vitro and in vivo [ 30 , 31 , 32 ]. Genetic suppression of Slit2 or overexpression of Robo1 in hepatocellular carcinoma promotes tumor growth and metastasis [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

Slit2/Robo1 signaling inhibits small‐cell lung cancer by targeting β‐catenin signaling in tumor cells and macrophages

et al. 2023

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Small‐cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with poor patient prognosis. However, the mechanisms that regulate SCLC progression and metastasis remain undefined. Here, we show that the expression of the slit guidance ligand 2 ( SLIT2 ) tumor suppressor gene is reduced in SCLC tumors relative to adjacent normal tissue. In addition, the expression of the SLIT2 receptor, roundabout guidance receptor 1 ( ROBO1 ), is upregulated. We find a positive association between SLIT2 expression and the Yes1 associated transcriptional regulator ( YAP1 )‐expressing SCLC subtype (SCLC‐Y), which shows a better prognosis. Using genetically engineered SCLC cells, adenovirus gene therapy, and preclinical xenograft models, we show that SLIT2 overexpression or the deletion of ROBO1 restricts tumor growth in vitro and in vivo . Mechanistic studies revealed significant inhibition of myeloid‐derived suppressor cells (MDSCs) and M2‐like tumor‐associated macrophages (TAMs) in the SCLC tumors. In addition, SLIT2 enhances M1‐like and phagocytic macrophages. Molecular analysis showed that ROBO1 knockout or SLIT2 overexpression suppresses the transforming growth factor beta 1 (TGF‐β1)/β‐catenin signaling pathway in both tumor cells and macrophages. Overall, we find that SLIT2 and ROBO1 have contrasting effects on SCLC tumors. SLIT2 suppresses, whereas ROBO1 promotes, SCLC growth by regulating the Tgf‐β1/glycogen synthase kinase‐3 beta (GSK3)/β‐catenin signaling pathway in tumor cells and TAMs. These studies indicate that SLIT2 could be used as a novel therapeutic agent against aggressive SCLC.

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Accelerated growth and local progression of radiorecurrent prostate cancer in an orthotopic bioluminescent mouse model

Frame,

Huang,

Haas

et al. 2024

Sci Rep

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ROBO1 protein expression is independently associated with biochemical recurrence in prostate cancer patients who underwent radical prostatectomy in Asian patients

Cited by 3 publications

References 25 publications

Parkinson’s Disease as a Risk Factor for Prostate Adenocarcinoma: A Molecular Point of View

Parkinson’s Disease as a Risk Factor for Prostate Adenocarcinoma: A Molecular Point of View

Slit2/Robo1 signaling inhibits small‐cell lung cancer by targeting β‐catenin signaling in tumor cells and macrophages

Accelerated growth and local progression of radiorecurrent prostate cancer in an orthotopic bioluminescent mouse model

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