Hypermethylation of MIR129-2 Regulates SOX4 Transcription and Associates with Metastasis in Patients with Colorectal Cancer

Soufiani, Alireza Rezayi; Dolatkhah, Roya; Raeisi, Mortaza; Chavoshi, Hadi; Mohammadi, Payam; Aghdam, Abdolreza Mehdinavaz

doi:10.1007/s12029-021-00708-9

Cited by 5 publications

(11 citation statements)

References 43 publications

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“… 17 Moreover, epigenetic inactivation by promoter hypermethylation was shown as a strategic survival mechanism of lymphoid hematological malignancies and a driver for colorectal cancer spread. 17 , 18 Nonetheless, most published studies on miRNAs biological function and its implication in ECa radioresistance were only performed in the ESCC subtype. 29 Thus, our results add significant information to this field, as we included a balanced series of EAC and ESCC.…”

Section: Discussionmentioning

confidence: 99%

“… 14 Moreover, miR129 promoter methylation was also reported in gastric cancer, hematological malignancies, and metastatic colorectal cancer. 16 , 17 , 18 In breast cancer, it is significantly associated with tumor progression and poor prognosis biomarker. 34 , 35 Specifically, cg14416371, a probe within miR129 CpG island which overlaps the one selected for our study, was previously used to identify pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Mechanistically, miR129‐2 has also been reported to play tumor suppressive roles by specific targeting SOX4 17 . Moreover, epigenetic inactivation by promoter hypermethylation was shown as a strategic survival mechanism of lymphoid hematological malignancies and a driver for colorectal cancer spread 17,18 . Nonetheless, most published studies on miRNAs biological function and its implication in ECa radioresistance were only performed in the ESCC subtype 29 .…”

Section: Discussionmentioning

confidence: 99%

“…Hence, upon careful and comprehensive in silico analysis, we sought to uncover and validate hypermethylated miRNAs promoters as novel ECa biomarkers that might allow for accurate and reliable of disease detection after neoadjuvant ChRT treatment. Remarkably, one of those markers—miR129‐2 methylation (miR129‐2 me )—has been previously reported in gastric, colorectal, and urothelial carcinomas, as well as in hematological malignancies 14,16–18 . Nonetheless, to the best of our knowledge, methylome‐related studies on this specific miRNA have not yet been reported for ECa, as well as for miR124‐3 me .…”

Section: Introductionmentioning

confidence: 89%

“…Remarkably, one of those markers—miR129‐2 methylation (miR129‐2 me )—has been previously reported in gastric, colorectal, and urothelial carcinomas, as well as in hematological malignancies. 14 , 16 , 17 , 18 Nonetheless, to the best of our knowledge, methylome‐related studies on this specific miRNA have not yet been reported for ECa, as well as for miR124‐3 me . Because in our previous study, ZNF569 me was the best performing biomarker, 7 it was included in the biomarkers panel tested in the present study.…”

Section: Introductionmentioning

confidence: 91%

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DNA methylation biomarkers accurately detect esophageal cancer prior and post neoadjuvant chemoradiation

et al. 2023

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Background Esophageal cancer (ECa) is associated with high mortality, mostly due to late diagnosis, precluding curativeintent surgery. Hence, neoadjuvant chemoradiation (ChRT) is recommended in most patients regardless of histological subtype. A proportion of these patients, however, achieve complete disease remission and might be spared of radical surgery. The lack of reliable, minimally invasive biomarkers able to detect post‐ChRT disease persistence is, nonetheless, a major drawback. We have previously shown that miRNA promotor methylation enables accurate cancer detection in tissues and liquid biopsies but has been seldom explored in ECa patients. Aims Herein, we sought to unveil and validate novel candidate biomarkers able to detect ECa prior and post ChRT. Materials and Methods Promoter methylation of miR129‐2, miR124‐3 and ZNF569 was assessed, using quantitative methylation‐specific PCR (qMSP), in tissue samples from normal esophagus, treatment‐naïve and post‐ChRT ECa, as well as in liquid biopsies from ECa patients. Results All genes disclosed significantly different promoter methylation levels between ECa and normal esophagus, accurately detecting post‐ChRT disease, especially for adenocarcinoma. Remarkably, miR129‐2me/ZNF569me methylation panel identified ECa in liquid samples with 53% sensitivity and 87% specificity. Discussion MiR129‐2me, miR124‐3me and ZNF569me accurately discriminate ECa, either pre‐ or post‐ChRT, from normal tissue, enabling ECa detection. Furthermore, circulalting methylation‐based biomarkers are promising minimally invasive tools to detect post‐ChRT residual ECa. Conclusion Overall, our results encourage the use of miRNA methylation biomarkers as accurate ECa detection tools as a novel approach for ChRT response monitoring.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 91%

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DNA methylation biomarkers accurately detect esophageal cancer prior and post neoadjuvant chemoradiation

et al. 2023

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Unravelling the Genetic and Epigenetic Symphony: A Narrative Review Exploring the Interplay in Etiologi of Microtia

Koento,

Reksodiputro,

Yosia

2023

j.maxilo

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Microtia, a congenital anomaly of the external ear, serves as a model to explore the intricate synergy between genetics and epigenetics in shaping phenotypic outcomes. Genetics, residing in DNA, provides the blueprint for development, while epigenetic modifications modulate gene expression without altering the DNA sequence. This comprehensive review delves into their combined influence on microtia's etiology, unravelling the significance of DNA methylation, histone modifications, and microRNAs in ear formation and their susceptibility to environmental cues. Genetic investigations encompass pedigree analysis and whole-exome sequencing, spotlighting pivotal genes like HOXA4 and CHST15. Syndromic associations underscore the multifaceted genetic underpinning of microtia. This dynamic interplay between genetics and epigenetics enriches our understanding of developmental anomalies, offering insights for tailored interventions and clinical strategies to manage this condition in a personalized manner. The continuous exploration of these interactions opens avenues for deciphering intricate developmental processes and expanding our comprehension of related anomalies.

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Lynch Syndrome Biopathology and Treatment: The Potential Role of microRNAs in Clinical Practice

Ascrizzi,

Arillotta,

Grillone

et al. 2023

Cancers

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Lynch syndrome (LS), also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is an autosomal dominant cancer syndrome which causes about 2–3% of cases of colorectal carcinoma. The development of LS is due to the genetic and epigenetic inactivation of genes involved in the DNA mismatch repair (MMR) system, causing an epiphenomenon known as microsatellite instability (MSI). Despite the fact that the genetics of the vast majority of MSI-positive (MSI+) cancers can be explained, the etiology of this specific subset is still poorly understood. As a possible new mechanism, it has been recently demonstrated that the overexpression of certain microRNAs (miRNAs, miRs), such as miR-155, miR-21, miR-137, can induce MSI or modulate the expression of the genes involved in LS pathogenesis. MiRNAs are small RNA molecules that regulate gene expression at the post-transcriptional level by playing a critical role in the modulation of key oncogenic pathways. Increasing evidence of the link between MSI and miRNAs in LS prompted a deeper investigation into the miRNome involved in these diseases. In this regard, in this study, we discuss the emerging role of miRNAs as crucial players in the onset and progression of LS as well as their potential use as disease biomarkers and therapeutic targets in the current view of precision medicine.

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Hypermethylation of MIR129-2 Regulates SOX4 Transcription and Associates with Metastasis in Patients with Colorectal Cancer

Cited by 5 publications

References 43 publications

DNA methylation biomarkers accurately detect esophageal cancer prior and post neoadjuvant chemoradiation

DNA methylation biomarkers accurately detect esophageal cancer prior and post neoadjuvant chemoradiation

Unravelling the Genetic and Epigenetic Symphony: A Narrative Review Exploring the Interplay in Etiologi of Microtia

Lynch Syndrome Biopathology and Treatment: The Potential Role of microRNAs in Clinical Practice

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