Epigenetic dysregulation-mediated COL12A1 upregulation predicts worse outcome in intrahepatic cholangiocarcinoma patients

Tang, Zengwei; Yang, Yuan; Zhang, Qi; Liang, Tingbo

doi:10.1186/s13148-022-01413-5

Cited by 7 publications

(31 citation statements)

References 46 publications

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“…COL12A1-high expression was associated with the poor prognoses of iCCA patients. Experimental knockout of COL12A1 inhibited the proliferation, invasiveness and growth of iCCA cells [ 77 ]. Jiali Li et al presented that METTL3 could promote cell proliferation, migration and invasion and upregulate the expression of COL12A1 in esophageal squamous cell carcinoma (ESCC) cell lines; besides, COL12A1 could restrain siMETTL3-mediated inhibition of proliferation, migration and invasion [ 78 ].…”

Section: Discussionmentioning

confidence: 99%

Jian Yun Qing Hua Decoction inhibits malignant behaviors of gastric carcinoma cells via COL12A1 mediated ferroptosis signal pathway

Liu,

Li,

et al. 2023

Chin Med

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Background Jian Yun Qing Hua Decoction (JYQHD), a traditional Chinese medicine decoction, which has been applied in the treatment of gastric cancer (GC). We attempt to confirm the anti-gastric cancer effect of JYQHD and explore the mechanism of JYQHD. Methods Acute toxicity test was used to understand the toxicity of JYQHD. We studied the expression and prognostic outcome of COL12A1 within GC tissues through the network databases. Using several web-based databases, we analyzed the major components and targets of JYQHD, as well as known therapeutic targets in gastric cancer. The Venn diagram was utilized to obtain the overlapped genes. Lentiviral vector, shRNAs and plasmids, were used to transfect GC cells. Cell counting kit-8 (CCK8), sphere formation, malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), Fe2+, transmission electron microscopy (TEM), quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), Western-Blot (WB), and immunohistochemical (IHC) assays were employed to investigate the role and mechanism of COL12A1 and JYQHD in GC. Results The results showed that JYQHD was non-toxic and safe. JYQHD inhibited growth and sphere formation ability through inducing the ferroptosis of GC cells, and suppressed the GC cells induced subcutaneous xenograft tumor growth. COL12A1 was highly expressed in gastric cancer tissues, indicating poor prognosis. COL12A1 specifically enhanced GC cell progression and stemness via suppressing ferroptosis. JYQHD down-regulated COL12A1 in order to suppress the stemness of GC cells via inducing ferroptosis. Conclusion COL12A1 inhibited ferroptosis and enhanced stemness in GC cells. JYQHD inhibited the development of GC cells by inhibiting cancer cell stemness via the ferroptosis pathway mediated by COL12A1.

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Section: Discussionmentioning

confidence: 99%

Jian Yun Qing Hua Decoction inhibits malignant behaviors of gastric carcinoma cells via COL12A1 mediated ferroptosis signal pathway

Liu,

Li,

et al. 2023

Chin Med

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“…DNAm alterations and gene expression changes in tissues from patients with heart failure (HF) have been identified, offering potential as diagnostic and therapeutic targets in HF ( 22 ). Additionally, collagen type XII alpha 1 chain has been acknowledged as a potential druggable site for the treatment of intrahepatic cholangiocarcinoma epigenetic ( 23 ). Again, DNAm alterations in the transcription factor 7-like 2 promoter region have been identified as a possible biomarker that can predict the diagnosis of type 2 diabetes ( 24 ).…”

Section: General Applications Of Dnam In Diseasesmentioning

confidence: 99%

Effects of DNA methylation and its application in inflammatory bowel disease (Review)

Akanyibah,

Zhu,

Wan

et al. 2024

Int J Mol Med

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Inflammatory bowel disease (IBD) is marked by persistent inflammation, and its development and progression are linked to environmental, genetic, immune system and gut microbial factors. DNA methylation (DNAm), as one of the protein modifications, is a crucial epigenetic process used by cells to control gene transcription. DNAm is one of the most common areas that has drawn increasing attention recently, with studies revealing that the interleukin (IL)-23/IL-12, wingless-related integration site, IL-6-associated signal transducer and activator of transcription 3, suppressor of cytokine signaling 3 and apoptosis signaling pathways are involved in DNAm and in the pathogenesis of IBD. It has emerged that DNAm-associated genes are involved in perpetuating the persistent inflammation that characterizes a number of diseases, including IBD, providing a novel therapeutic strategy for exploring their treatment. The present review discusses DNAm-associated genes in the pathogenesis of IBD and summarizes their application as possible diagnostic, prognostic and therapeutic biomarkers in IBD. This may provide a reference for the particular form of IBD and its related methylation genes, aiding in clinical decision-making and encouraging therapeutic alternatives.

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“…Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive malignancy with an extremely poor outcome. 1 – 3 The incidence and mortality of iCCA are increasing worldwide in recent years. 4 Most iCCA patients are typically detected at an advanced stage when the currently available systemic therapies have limited effectiveness since there is a lack of tumor-specific biomarkers for early detection of iCCA.…”

Section: Introductionmentioning

confidence: 99%

“… 4 Most iCCA patients are typically detected at an advanced stage when the currently available systemic therapies have limited effectiveness since there is a lack of tumor-specific biomarkers for early detection of iCCA. 3 , 5 …”

Section: Introductionmentioning

confidence: 99%

Epigenetic deregulation of MLF1 drives intrahepatic cholangiocarcinoma progression through EGFR/AKT and Wnt/β-catenin signaling

Tang

Yang

Chen

et al. 2023

Hepatology Communications

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Background: Intrahepatic cholangiocarcinoma (iCCA) is an aggressive malignancy with multiple etiologies and is largely refractory to current treatment strategies. Myeloid leukemia factor 1 (MLF1) is associated with human cancer progression. Nevertheless, the function of MLF1 in iCCA remains unknown. Methods: We performed expression analyses of MLF1 in human iCCA. In vitro and in vivo experiments were conducted to investigate the role of MLF1 in iCCA progression. The upstream regulatory mechanism of MLF1 upregulation in iCCA was deciphered by luciferase and DNA methylation analyses. Results: MLF1 was significantly upregulated in clinical iCCA tissue specimens and human iCCA cell lines. MLF1 was positively correlated with KRT19 and MUC1 expression and epithelial-mesenchymal transition (EMT) gene set enrichment score in clinical iCCA. High MLF1 expression was independently associated with worse prognoses in iCCA patients after curative resection. In addition, experimental knockdown of MLF1 attenuated, while overexpression of MLF1 promoted the proliferation, invasiveness, and growth of iCCA cells in vitro and in vivo. Mechanically, MLF1 comodulated EGFR/AKT and Wnt/β-catenin signalings through regulating EGFR, AKT, WNT3, and p-GSK3β expression. Promoter CpG sites’ hypermethylation-induced downregulation of miR-29c-3p contributed to MLF1 upregulation in iCCA patients. The upregulation of DNA methyltransferase (DNMT)1, 3A, and 3B downregulated miR-29c-3p by dictating promoter DNA methylation pattern. MiR-29c-3p showed therapeutic potential by targeting MLF1 in iCCA. Conclusions: Our results demonstrated that hypermethylation-mediated miR-29c-3p downregulation contributes to MLF1 upregulation in iCCA, which resulted in tumor cells’ proliferation and metastasis through comodulating EGFR/AKT and Wnt/β-catenin signalings.

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Epigenetic dysregulation-mediated COL12A1 upregulation predicts worse outcome in intrahepatic cholangiocarcinoma patients

Cited by 7 publications

References 46 publications

Jian Yun Qing Hua Decoction inhibits malignant behaviors of gastric carcinoma cells via COL12A1 mediated ferroptosis signal pathway

Jian Yun Qing Hua Decoction inhibits malignant behaviors of gastric carcinoma cells via COL12A1 mediated ferroptosis signal pathway

Effects of DNA methylation and its application in inflammatory bowel disease (Review)

Epigenetic deregulation of MLF1 drives intrahepatic cholangiocarcinoma progression through EGFR/AKT and Wnt/β-catenin signaling

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