Impact of RASSF1A gene methylation on clinico-pathological features of tumor and non-tumor tissue of breast cancer

Gupta, V.; Agarwal, P.; Deshpande, Prajakta

doi:10.1016/j.anndiagpath.2021.151722

Cited by 17 publications

(16 citation statements)

References 13 publications

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“…Previous studies regarding the Mst2 kinase reported that phosphorylation of Akt prevents Rassf1A binding and decreases Mst2 kinase activity (138,139). Rassf1A is a Hippo signaling pathway regulator that is highly silenced in human gastric (130), esophageal (140), lung (141), breast (142) and liver cancer (143). Akt signaling inhibition using a PI3K inhibitor can demethylate the promoter of Rassf1A and increase the protein expression levels of rassf1a, resulting in Hippo signaling pathway activation (144,145).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway

Meng

Nguyen

et al. 2022

Mol Med Rep

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colorectal cancer (crc) is one of the deadliest malignant tumors worldwide and its prevalence is increasing in South Korea. The efficacy of combined treatment with natural product-derived and chemotherapy agents including curcumin combined with 5-fluorouracil, resveratrol combined with cisplatin and epigallocatechin-3-gallate (EGCG) combined with cisplatin in preventing cancer progression and killing cancer cells has emerged. The akt and Hippo signaling pathways serve a key role in colorectal tumor growth; however, the exact role of the crosstalk between Akt and Hippo signaling pathways in CRC remains poorly elucidated. The combined effect of ua and doX on the cell proliferation, apoptosis, migration and cell cycle of CRC cells were investigated by performing Cell proliferation assay, a soft agar colony formation assay, flow cytometry, wound healing assay and western blotting assay. Subsequently, the expression of AKT and Hippo signaling pathway-associated proteins were also assessed by western blot assay. Moreover, a xenograft nude mouse model was constructed to verify the effects of UA and doX on the tumorigenesis of HcT116 cell in vivo. The present study reported that ursolic acid (UA) strongly enhanced the antitumor action of doxorubicin (DOX) via blocking the akt/glycogen synthase kinase-3β (Gsk3β) signaling pathway and activating tumor-suppressive Hippo signaling (mammalian Ste20-like kinase 1 and 2, salvador family WW domain containing protein 1 and MOB kinase activator 1), thereby downregulating downstream effector yes-associated protein 1 (Yap) and connective tissue growth factor (cTGF) protein expression levels in CRC cells. Furthermore, The PI3K inhibitor LY294002 further suppressed Akt activity and enhance the function of Hippo pathway-associated proteins in DOX + UA treated cells; this effect led to subsequent oncogenic Yap and CTGF inhibition following combined treatment, whereas akt activator Sc79 exerted an opposite effect in cTGF expression. In vivo, treatment with UA combined with DOX markedly suppressed the progression of CRC without any toxic effects on a xenograft mouse model by disrupting Akt signaling and activating the Hippo signaling pathway. These results demonstrated that UA and DOX treatment successfully induced akt/Gsk3β inactivation via Hippo signaling pathway activation to promote Yap degradation, resulting in the inhibition of colorectal tumorigenesis. In conclusion, these findings suggested that combination therapy with UA and DOX may be more effective than DOX alone. UA may be a novel anticancer strategy and could be considered for investigation as a complementary chemotherapy agent in the future.

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Section: Discussionmentioning

confidence: 99%

Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway

Meng

Nguyen

et al. 2022

Mol Med Rep

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“…Although RASSF1A remains expressed in cancer, concentrations of RASSF1A protein above or below its optimal expression threshold can disrupt signal transduction and lead to malignant transformation [ 31 ]. Promoter methylation of RASSF1A was also found to be significantly correlated with tumor size and histological grade of BC [ 33 ]. Therefore, we hypothesized that hypermethylation of RASSF1A promoter disrupts normal body signal transduction, leading to tumor recurrence, and metastasis and poorer clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Correlation between RASSF1A Methylation in Cell-Free DNA and the Prognosis of Cancer Patients: A Systematic Review and Meta-Analysis

Chen

Duan

Zhang

et al. 2022

Journal of Oncology

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Background. Although the effects of methylation of the Ras association domain-containing protein 1 isoform A (RASSF1A) gene in cell-free DNA on the outcomes of patients with different types of cancer have been reported, the results are inconsistent. Objective: To explore the relationships between RASSF1A methylation in cell-free DNA and the outcomes of cancer patients. Methods. The PubMed, Embase, and Web of Science databases were searched for papers related to this topic on December 8, 2021. The retrieved articles were screened by two independent researchers, following which the methodological quality of the selected studies was evaluated using the Newcastle-Ottawa Scale. Additionally, hazard ratios were calculated, and publication bias of the studies was determined using Egger’s test. Results. Nine relevant publications involving a combined total of 1254 patients with different types of cancer were included in this study. The combined results of the random effects models yielded a hazard ratio of 1.73 (95% confidence interval: 1.31, 2.29; P < 0.001 ), which suggested there was a significant association between RASSF1A methylation and overall survival, and patients with an RASSF1A methylation status had a significantly increased risk of total death. Moreover, the Egger test result suggested there was no significant publication bias among the included studies. Conclusions. The methylation of RASSF1A in cell-free DNA in cancer patients was observably associated with an increased risk of poor overall survival.

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“…You may be limited in your activities depending on the extent and severity of the disease. To prevent future infection, your healthcare professional may recommend that you take treatment for a long time [12,13,14].…”

Section: Discussionmentioning

confidence: 99%

“…Brainstem gliomas have an incidence rate of 1.4 percent of intracranial tumors in the child age group and comprise 28.7 percent of posterior fossa tumors in the child age group. The exact incidence of brainstem glioma is not known due to low biopsy of tissue and resection rates of these lesions [15,16,17].…”

Section: Discussionmentioning

confidence: 99%

A Rare Case of Anaplastic Astrocytoma

Durgam

Ghungrud

Alwadkar

et al. 2021

JPRI

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Introduction: In adult’s glioblastoma is the most common malignant tumor, which occurs due to the abnormal growth of astrocytes cells. Slightly it is more common in men than females. Standard and quality of care and advanced treatment make a positive impact on patients’ quality of life. However, glioblastoma cannot be cured completely, but treatment approaches such as radiation and chemotherapy may improve the clinical course, but these treatments often takes a heavy toll. Case Presentation: Here we are reporting about a 45 -years-old male who is admitted to Acharya Vinoba Bhave Rural Hospital. With the complaints of headache, for 1 year, history of seizure 2 episodes 3 months before then patient is on antiepileptic medication. Patient was conscious with altered mental status. By radiological investigation, it was revealed that there was a right occipital region glioma tradition necrosis was present. In his family, there was no history of hypertension, diabetes mellitus. On physical examination, s1 and s2 sounds were present and it was normal. The tumor was invading the parenchyma of the right transverse sinus. Dura opened in a cruciate manner, the tumor decompress internally which was vascular, and suck able tumor base interface found. Then patient underwent malignant glioma excision i.e., gross total resection of the tumor was done under general anesthesia. After that, he managed with antibiotics, analgesics, antiepileptic, and anti-edema, now the patient was neurologically stable and he was shifted toward. His histopathology report shows anaplastic astrocytoma. Now patient was in stable condition. Hence being discharged with follow-up after 15 days in Neuro OPD. Conclusion: Glioma is a brain tumor that affects the human body. There is a poor prognosis of this disease and survival time, therapy is limited. But early diagnosis and treatment patients can spend quality of life.

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Impact of RASSF1A gene methylation on clinico-pathological features of tumor and non-tumor tissue of breast cancer

Cited by 17 publications

References 13 publications

Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway

Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway

Correlation between RASSF1A Methylation in Cell-Free DNA and the Prognosis of Cancer Patients: A Systematic Review and Meta-Analysis

A Rare Case of Anaplastic Astrocytoma

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