RASSF1A: A promising target for the diagnosis and treatment of cancer

Bin, Yuling; Ding, Yong; Xiao, Weisheng; Liao, Aijun

doi:10.1016/j.cca.2020.01.014

Cited by 10 publications

(6 citation statements)

References 167 publications

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“…Recently, epigenetic genes, as tumor suppressors frequently silenced by hypermethylation, have attracted considerable attention as potential biomarkers owing to their anticancer effect. Among these epigenetic genes, RASSF1A has been shown to be hypermethylated in various malignancies; in addition, it acts as a regulator or effector of multiple cancer signaling pathways, driving tumorigenesis and progression of solid cancers (García‐Gutiérrez et al, 2022), including GC (Bin et al, 2020). In a previous study, RASSF1A was shown to inhibit cell proliferation and induce cell cycle arrest in GC (Liao et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, abnormal expression of RASSF1A has been implicated in tumor invasion, metastasis, and other biological processes via regulation of apoptosis, cell cycle arrest, mitotic arrest, and migration (Garcia‐Gutierrez et al, 2020). Several studies have demonstrated the clinical relevance of RASSF1A as a diagnostic and prognostic marker as well as for monitoring the therapeutic effect in cancer patients (Bin et al, 2020; Chen et al, 2022). We have earlier shown that RASSF1A arrests GC cells in the G1 phase by upregulating the expression of miR‐711 (Liao et al, 2016a).…”

Section: Introductionmentioning

confidence: 99%

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RASSF1A inhibits epithelial–mesenchymal transition of gastric cancer cells by downregulating P‐JNK

Bin

Deng

et al. 2022

Cell Biology International

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Gastric cancer (GC) is one of the most common gastrointestinal tumors. In this study, we assessed the biological role of Ras association domain family 1 isoform A (RASSF1A) in GC cells. Expressions of RASSF1A and the relationship of RASSF1A with epithelial–mesenchymal transformation (EMT)‐related proteins were assessed in five cell lines using Western blot. GC cells with RASSF1A overexpression were used to study sensitivity to cisplatin, migration, invasion, and the expression of EMT‐associated biomarkers. GC cells showed profound downregulation of RASSF1A expression compared with normal human gastric mucosal cells. High RASSF1A expression was associated with increased overall survival. Overexpression of RASSF1A regulates GC cells activity and the expression of EMT‐associated biomarkers. RASSF1A regulates E‐cadherin and Vimentin through P‐JNK pathway. Our results revealed that RASSF1A can inhibit the proliferation, migration, and invasion of GC cells via E‐cadherin. Our study provides insights for further research on GC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RASSF1A inhibits epithelial–mesenchymal transition of gastric cancer cells by downregulating P‐JNK

Bin

Deng

et al. 2022

Cell Biology International

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“…Since this epigenetic modification is very common in a wide range of cancers, RASSF1A targeted therapies are currently in the developmental phase. [35][36][37] Thus, investigating the potential efficiency of this therapy in MB can provide useful information for treatment protocols.…”

Section: Discussionmentioning

confidence: 99%

Gene-Specific DNA Methylation Profiles in Pediatric Medulloblastomas

et al. 2021

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Introduction Medulloblastoma is the most common pediatric central nervous tumor of high malignancy that has been classified into both histological subtypes and molecular subgroups by the 2016 World Health Organization classification. However, there is a still need to understand the genomic characteristics and predict the clinical course. The aim of the study is to investigate the significance of the methylation profiles in molecular subclassification and precision medicine of the disease. Methods The study enrolled 47 pediatric medulloblastoma patients. DNA methylation levels of KLF4, SPINT2, RASSF1A, EZH2, ZIC2, and PTCH1 genes were analyzed using methylation-specific pyrosequencing. The significance of the statistical relationship between methylation profiles and clinicopathological parameters including molecular subgroups and histological subtypes, the status of metastasis, and event-free survival were analyzed. Results DNA methylation analysis demonstrated that KLF4, PTCH1, and ZIC2 hypermethylation were associated with the SHH-activated subgroup, whereas both SPINT2 and RASSF1A hypermethylation were associated with metastatic disease. EZH2 gene was not methylated in any of the samples. Conclusion We think that customized DNA methylation profiling may be a useful tool in the molecular subclassification of pediatric medulloblastoma and a potential technical approach in precision medicine.

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“…Furthermore, as we also applied in the current study, an enzyme-based ddPCR for methylated RASSF1A in cfDNA is also suited for the detection of tumor-derived cfDNA. Since hypermethylation of RASSF1A has been found in many types of tumors (54)(55)(56)(57)(58)(59)(60), this assay offers another approach for liquid biopsybased disease monitoring. The combination of both RNA and DNAbased platforms for the analysis of liquid biopsies could be complementary, as we have showed previously in a cohort of patients with rhabdomyosarcoma (61).…”

Section: A B Cmentioning

confidence: 99%

Targeted locus amplification to develop robust patient-specific assays for liquid biopsies in pediatric solid tumors

et al. 2023

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BackgroundLiquid biopsies combine minimally invasive sample collection with sensitive detection of residual disease. Pediatric malignancies harbor tumor-driving copy number alterations or fusion genes, rather than recurrent point mutations. These regions contain tumor-specific DNA breakpoint sequences. We investigated the feasibility to use these breakpoints to design patient-specific markers to detect tumor-derived cell-free DNA (cfDNA) in plasma from patients with pediatric solid tumors.Materials and methodsRegions of interest (ROI) were identified through standard clinical diagnostic pipelines, using SNP array for CNAs, and FISH or RT-qPCR for fusion genes. Using targeted locus amplification (TLA) on tumor organoids grown from tumor material or targeted locus capture (TLC) on FFPE material, ROI-specific primers and probes were designed, which were used to design droplet digital PCR (ddPCR) assays. cfDNA from patient plasma at diagnosis and during therapy was analyzed.ResultsTLA was performed on material from 2 rhabdomyosarcoma, 1 Ewing sarcoma and 3 neuroblastoma. FFPE-TLC was performed on 8 neuroblastoma tumors. For all patients, at least one patient-specific ddPCR was successfully designed and in all diagnostic plasma samples the patient-specific markers were detected. In the rhabdomyosarcoma and Ewing sarcoma patients, all samples after start of therapy were negative. In neuroblastoma patients, presence of patient-specific markers in cfDNA tracked tumor burden, decreasing during induction therapy, disappearing at complete remission and re-appearing at relapse.ConclusionWe demonstrate the feasibility to determine tumor-specific breakpoints using TLA/TLC in different pediatric solid tumors and use these for analysis of cfDNA from plasma. Considering the high prevalence of CNAs and fusion genes in pediatric solid tumors, this approach holds great promise and deserves further study in a larger cohort with standardized plasma sampling protocols.

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RASSF1A: A promising target for the diagnosis and treatment of cancer

Cited by 10 publications

References 167 publications

RASSF1A inhibits epithelial–mesenchymal transition of gastric cancer cells by downregulating P‐JNK

RASSF1A inhibits epithelial–mesenchymal transition of gastric cancer cells by downregulating P‐JNK

Gene-Specific DNA Methylation Profiles in Pediatric Medulloblastomas

Targeted locus amplification to develop robust patient-specific assays for liquid biopsies in pediatric solid tumors

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