Transcription Factors and Methylation Drive Prognostic miRNA Dysregulation in Hepatocellular Carcinoma

Qin, Si; Xu, Jieyun; Yi, Yunmeng; Jiang, Sizhu; Park, Jin; Xia, Xinyi; Ma, Fei

doi:10.3389/fonc.2021.691115

Cited by 10 publications

(5 citation statements)

References 81 publications

(96 reference statements)

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“…The dysregulation of miRNAs is common in cancers and is caused by various mechanisms, including mutations involving miRNA loci, epigenetic silencing, and transcription factor dysregulation [ 6 , 7 , 8 , 9 , 10 ]. Through sRNA sequencing, we confirmed that hsa-miR-100-5p is downregulated in several HCC cell lines, which suggests a close association between hsa-miR-100-5p dysregulation and HCC.…”

Section: Discussionmentioning

confidence: 99%

“…MicroRNAs (miRNAs) are small endogenous single-stranded non-coding RNAs that have been recognized as playing essential roles in cancer prognosis by regulating a wide range of biological processes, typically via sequence-specific RNA-RNA interactions [ 5 , 6 ]. Due to various mutations, miRNAs are heavily dysregulated in cancer cells, leading to the dysregulation of multiple protein-coding oncogenes [ 6 , 7 , 8 , 9 , 10 ]. miRNAs are crucial regulators in the development and progression of HCC [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Increased hsa-miR-100-5p Expression Improves Hepatocellular Carcinoma Prognosis in the Asian Population with PLK1 Variant rs27770A>G

Liao,

Zhang,

Yang

et al. 2023

Cancers

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Hepatocellular carcinoma (HCC) has the highest incidence and mortality in the Asian population, and race is an independent risk factor affecting survival time in liver cancer. Micro RNAs (miRNAs) are remarkably dysregulated in HCC and closely associated with HCC prognosis. Recent studies show that genetic variability between ethnic groups may result in differences in the specificity of HCC miRNA biomarkers. Here, we reveal a high expression level of hsa-miR-100-5p, an HCC prognosis-related miRNA, which improves HCC prognosis in the Asian Population with Polo-like kinase 1 (PLK1) variant rs27770A>G. In this study, we discovered that hsa-miR-100-5p was downregulated in various HCC cell lines. While mimics transient transfection and mouse liver cancer model confirmed the interaction between hsa-miR-100-5p and PLK1, a stratified analysis based on the Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) data suggest both low hsa-miR-100-5p expression level and high PLK1 expression level associated with poor HCC prognosis, especially in the Asian population. According to the 1000 Genomes Project database, the SNP rs27770 located in 3′UTR of PLK1 had a significantly higher G allele frequency in the East Asian population. Bioinformatics analysis suggested that rs27770 A>G affects PLK1 mRNA secondary structure and alters the hsa-miR-100-5p/PLK1 interaction by forming an additional seedless binding site. This racial variation caused PLK1 to be more vulnerable to hsa-miR-100-5p inhibition, resulting in hsa-miR-100-5p being more favorable for HCC prognosis in the Asian population.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased hsa-miR-100-5p Expression Improves Hepatocellular Carcinoma Prognosis in the Asian Population with PLK1 Variant rs27770A>G

Liao,

Zhang,

Yang

et al. 2023

Cancers

View full text Add to dashboard Cite

show abstract

“…It was found that the AUC values of miRNA-452-5p, miRNA-5589-5p, miRNA-5589-3p, and miRNA-4661-5p in the early diagnosis of HCC were 0.830, 0.879, 0.838, and 0.725, respectively. Moreover, the four miRNAs were differentially expressed in only one or two types of cancer with good specificity, which might be used as the early diagnostic biomarkers for HCC [ 62 ]. In addition, Huang et al found that miRNAs might also serve as the diagnostic biomarkers for lung metastasis in HCC patients, and the combination of multiple miRNAs had better performance than a single miRNA.…”

Section: Mirnas and Cancer Diagnosis And Prognosismentioning

confidence: 99%

Overview of MicroRNAs as Diagnostic and Prognostic Biomarkers for High-Incidence Cancers in 2021

Sun

Zhao

Wang

et al. 2022

IJMS

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MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) about 22 nucleotides in size, which play an important role in gene regulation and are involved in almost all major cellular physiological processes. In recent years, the abnormal expression of miRNAs has been shown to be associated with human diseases including cancer. In the past ten years, the link between miRNAs and various cancers has been extensively studied, and the abnormal expression of miRNAs has been reported in various malignant tumors, such as lung cancer, gastric cancer, colorectal cancer, liver cancer, breast cancer, and prostate cancer. Due to the high malignancy grade of these cancers, it is more necessary to develop the related diagnostic and prognostic methods. According to the study of miRNAs, many potential cancer biomarkers have been proposed for the diagnosis and prognosis of diseases, especially cancer, thus providing a new theoretical basis and perspective for cancer screening. The use of miRNAs as biomarkers for diagnosis or prognosis of cancer has the advantages of being less invasive to patients, with better accuracy and lower price. In view of the important clinical significance of miRNAs in human cancer research, this article reviewed the research status of miRNAs in the above-mentioned cancers in 2021, especially in terms of diagnosis and prognosis, and provided some new perspectives and theoretical basis for the diagnosis and treatment of cancers.

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“…For instance, miR-1292-5p and miR-1301-3p helped regulate cell proliferation and epithelial–mesenchymal transformation (EMT) of common tumors in general surgery (e.g., thyroid cancer and gastric cancer). , miR-3614-5p could act as an antiviral and a regulator of human primary macrophages, thereby controlling dengue viral replication . Furthermore, miR-5589-3p could be one of the vital methylation drivers and transcription factors in liver cancer …”

Section: Introductionmentioning

confidence: 99%

“…19 Furthermore, miR-5589-3p could be one of the vital methylation drivers and transcription factors in liver cancer. 20 With the development of modern medical technology, researchers have more stringent requirements for the molecules that can be used for visual observation. Many optical nanoprobes are available, including organic smallmolecule dyes, fluorescent proteins, and inorganic quantum dots, 21−24 which are used as the primary carrier tools for biomedical imaging and play an essential part in basic scientific research; clinical laboratory examination; and interpretation, diagnosis and prognostic evaluation of diseases.…”

Section: ■ Introductionmentioning

confidence: 99%

Monitoring Clinical–Pathological Grading of Hepatocellular Carcinoma Using MicroRNA-Guided Semiconducting Polymer Dots

Zhang

Lin

et al. 2022

ACS Appl. Mater. Interfaces

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MicroRNAs (miRNAs) are a class of small, noncoding RNAs involved in nearly all genetic central dogma processes and human biological behavior, which also play a significant role in the pathological activity of tumors, such as gene transcription, protein translation, and exosome secretion. Therefore, through the navigation of certain specific miRNAs, we can trace the specific physiological processes or image some specific tissues. Designing and accurately positioning microRNA (miRNA)-sensitive fluorescent nanoprobes with benign specificity and recognition in cells or tissues are a challenging research field. To solve the difficulties, we introduce four semiconducting polymer dots (Pdots) as nanoprobes linked by specific miRNA antisense sequences for monitoring the pathological grading by the variation in miRNA expression. Based on the base pairing principle, these miRNAsensitive Pdots could bind to specific miRNAs within the cancerous cells. As impacted by the background of different pathology gradings, the proportions of the four hepatocellular carcinoma (HCC)-specific miRNAs within the cancerous cell are different, and the pathological grading of the patient tissues can be determined by comparing the palette combinations. The short single-stranded RNA-functionalized Pdots, which have excellent microRNA sensitivity, are observed in an experimental cell model and a series of tissue specimens from HCC patients for the first time. Using the Forster (or fluorescence) resonance energy transfer (FRET) model of Pdots and Cy3dt tag to simulate in vivo miRNA detection, the superior sensitivity and specificity of these nanoprobes are verified. The interference of subjective factors in traditional single/bis-dye emission intensity detection is abandoned, and multiple label staining is used to enhance sensitivity further and reduce the false-positive rate. The feasibility exhibited by this novel staining method is verified in normal hepatocellular HCC cell lines and 16 frozen ultrathin tissue sections, which are employed to quantify pathological grading-related color presentation systems for clinical doctors and pathologists' use. The intelligently designed miRNAguided Pdots will emerge as an ideal platform with promising biological imaging.

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Transcription Factors and Methylation Drive Prognostic miRNA Dysregulation in Hepatocellular Carcinoma

Cited by 10 publications

References 81 publications

Increased hsa-miR-100-5p Expression Improves Hepatocellular Carcinoma Prognosis in the Asian Population with PLK1 Variant rs27770A>G

Increased hsa-miR-100-5p Expression Improves Hepatocellular Carcinoma Prognosis in the Asian Population with PLK1 Variant rs27770A>G

Overview of MicroRNAs as Diagnostic and Prognostic Biomarkers for High-Incidence Cancers in 2021

Monitoring Clinical–Pathological Grading of Hepatocellular Carcinoma Using MicroRNA-Guided Semiconducting Polymer Dots

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