Current Understanding of Epigenetics Driven Therapeutic Strategies in Colorectal Cancer Management

Deka, Dikshita; Scarpa, Marco; Das, Alakesh; Pathak, Surajit; Banerjee, Antara

doi:10.2174/1871530321666210219155544

Cited by 8 publications

(4 citation statements)

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“…Patients with CRC are prone to regional lymph node metastasis in the early stage. Tumors spread to lymph nodes through lymphatic vessels, making treatment difficult for patients and the high mortality [ 26 ]. The liver is also the site where CRC patients are prone to metastases.…”

Section: Discussionmentioning

confidence: 99%

Expression Levels and Clinical Significance of Serum miR-497, CEA, CA24-2, and HBsAg in Patients with Colorectal Cancer

Liu

Chen

2022

BioMed Research International

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The objective of the current study was to look at the levels of blood micro ribonucleic acid- (miR-) 497, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 24-2, and hepatitis B surface antigen (HBsAg) in patients with colorectal cancer (CRC), as well as the clinical importance of these markers in CRC patients. The serum levels of miR-497, CEA, CA24-2, and HBsAg were compared between 60 patients with CRC (observation group) and another 60 patients with colorectal polyps (control group). The 4 indicators in patients with lymph node metastasis and liver metastasis were compared. The diagnostic effects of 4 detection methods and the combined detection were analyzed, and the influence of 4 indicators on the 5-year cumulative survival rate of patients was discussed. The results showed that the serum levels of miR-497 and HBsAg were lower, and the levels of CEA and CA24-2 were higher in the observation group ( P < 0.05 ). The combined detection had the best diagnostic effect, and CEA alone had the best prediction effect. The serum level of miR-497 was significantly lower in patients with lymphatic metastasis, with the significantly higher levels of CEA and CA24-2 ( P < 0.05 ). The HBsAg level of patients with liver metastases was greatly lower than that of patients without liver metastases ( P < 0.05 ). The 5-year cumulative survival rate of patients with high levels of CEA and CA24-2 was significantly lower than that of patients with low level of CEA. The 5-year cumulative survival rate was lower in patients with low level of HBsAg, but the difference was small. The 5-year cumulative survival rate of patients with elevated serum miR-497 was observably lower. In conclusion, combined detection could diagnose CRC more accurately. Serum miR-497, CEA, and CA24-2 were important in the diagnosis of lymph node metastasis of CRC. HBsAg did a better job of predicting liver metastases in CRC patients. High level of CEA significantly reduced the cumulative survival rate of CRC patients and could predict the long-term survival rate of patients. Serum levels of miR-497, CEA, CA24-2, and HBsAg played a positive role in the diagnosis and evaluation of CRC and could identify lymph node and liver metastases, having a high clinical guidance value.

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Section: Discussionmentioning

confidence: 99%

Expression Levels and Clinical Significance of Serum miR-497, CEA, CA24-2, and HBsAg in Patients with Colorectal Cancer

Liu

Chen

2022

BioMed Research International

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“…CRC is a heterogeneous disease with different gene expression patterns and the identification of genetic molecular markers may be conducive to predict the prognosis of CRC and provide an alternative treatment option for CRC (25)(26)(27). ENO1 is a multifunctional protein that has been revealed to be aberrantly expressed in multiple human malignancies, such as breast cancer, gastric cancer, head and neck cancer, and to be related to the disease progression (10).…”

Section: Discussionmentioning

confidence: 99%

ENO1 deletion potentiates ferroptosis and decreases glycolysis in colorectal cancer cells via AKT/STAT3 signaling

Liu,

Hou,

Zhang

et al. 2024

Exp Ther Med

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Colorectal cancer (CRC) is one of the most prevailing and lethal forms of cancer globally. α-enolase (ENO1) has been well documented to be involved in the progression and drug resistance of CRC. The present study was designed to specify the role of ENO1 in major events during the process of CRC and to introduce its latent functional mechanism. ENO1 expression was determined by western blot analysis. Extracellular acidification rates were assessed using an XF96 extracellular flux analyzer. Glucose uptake, lactic acid production, total iron levels and ferroptosis-related markers were examined with corresponding kits. A dichlorodihydrofluorescein diacetate probe measured intracellular reactive oxygen species content. Western blotting detected the expression of glycolysis- and ferroptosis-related proteins. CCK-8 and EdU staining assays assessed cell proliferation. In the current study, ENO1 was highly expressed in CRC cells. Knockdown of ENO1 markedly reduced the glycolysis and accelerated the ferroptosis in CRC cells. Moreover, the inhibitory effects of WZB117, a specific inhibitor of glycolysis-related glucose transporter type 1, on CRC cell proliferation were further enhanced by ENO1 interference. In addition, silencing of ENO1 inactivated the AKT/STAT3 signaling. The AKT activator SC79 partially reversed the effects of ENO1 deficiency on the AKT/STAT3 signaling, glycolysis, proliferation as well as ferroptosis in CRC cells. In summary, inactivation of AKT/STAT3 signaling mediated by ENO1 inhibition might boost the ferroptosis and suppress the glycolysis in CRC cells.

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“…miR-19a-3p is actively involved in colon cancer proliferation, invasion, and migration of colon cancer by targeting T cell intracellular antigen 1; thus, it could represent a prognostic biomarker (Ardizzone et al 2021 ). MiR-19a is a well-known oncogenic miRNA among the miR-19 family members, and its overexpression has been linked to cell proliferation, invasion, migration, metastasis, tumor size, stage of development, and poor prognosis (Deka et al 2021 ; Jothimani et al 2018 ). As a result, miR-19a is believed to be a potential biomarker and potential therapeutic target for diagnostic and prognostic applications.…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Study on the Anti-cancer Effects of Quercetin and Its Epigenetic Modifications in Arresting Progression of Colon Cancer Cell Proliferation

Bhatiya

Pathak

Jothimani

et al. 2023

Arch. Immunol. Ther. Exp.

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Colon cancer etiology involves a wide spectrum of genetic and epigenetic alterations, finding it challenging to find effective therapeutic strategies. Quercetin exhibits potent anti-proliferative/apoptotic properties. In the present study, we aimed to elucidate the anti-cancer and anti-aging effect of quercetin in colon cancer cell lines. The anti-proliferative effect of quercetin was assessed in vitro by CCK-8 in normal and colon cancer cell lines. To check the anti-aging potential of quercetin, collagenase, elastase, and hyaluronidase inhibitory activity assays were performed. The epigenetic and DNA damage assays were performed using the human NAD-dependent deacetylase Sirtuin-6, proteasome 20S, Klotho, Cytochrome-C, and telomerase ELISA kits. Furthermore, the aging-associated miRNA expression profiling was performed on colon cancer cells. The treatment with quercetin inhibited cell proliferation of colon cancer cells in a dose-dependent manner. Quercetin arrested colon cancer cell growth by modulating expression of aging proteins including Sirtuin-6 and Klotho and also by inhibiting telomerase activity to restrict the telomere length which is evident from qPCR analysis. Quercetin also exhibited DNA damage protection by reducing proteasome 20S levels. The miRNA expression profiling results displayed differential expression of miRNA in colon cancer cell, and in addition, the highly upregulated miRNA was involved in the regulation of cell cycle, proliferation, and transcription. Our data suggest that quercetin treatment inhibited cell proliferation in colon cancer cells through regulating the anti-aging protein expression and provides better understanding for quercetin’s potential use in colon cancer treatment.

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Current Understanding of Epigenetics Driven Therapeutic Strategies in Colorectal Cancer Management

Cited by 8 publications

References 0 publications

Expression Levels and Clinical Significance of Serum miR-497, CEA, CA24-2, and HBsAg in Patients with Colorectal Cancer

Expression Levels and Clinical Significance of Serum miR-497, CEA, CA24-2, and HBsAg in Patients with Colorectal Cancer

ENO1 deletion potentiates ferroptosis and decreases glycolysis in colorectal cancer cells via AKT/STAT3 signaling

A Comprehensive Study on the Anti-cancer Effects of Quercetin and Its Epigenetic Modifications in Arresting Progression of Colon Cancer Cell Proliferation

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