• cancer etiology
• esophageal cancer
• esophageal squamous cell carcinoma

• 18192061; 20211551 Health and Medical Research Fund (HMRF) from the Food and Health Bureau (FHB) of The Government of the Hong Kong Special Administrative Region
• T24-508/22-N Theme-based Research Scheme (TRS) of the Hong Kong Research Grants Council
• 82173469 General Program of National Natural Science Foundation of China
• 2022A1515011151 Guangdong Natural Science Fund (GD-NSF) of China
• 102010191 Seed Funding for Strategic Interdisciplinary Research Scheme from the University Research Com-mittee at the University of Hong Kong
• 17613819, 17115122, 17109723 General Research Fund (GRF) scheme from the Research Grants Council of the Hong Kong Special Administrative Region

• disease susceptibility
• gene mutation
• hereditable disease
• phosphotyrosine
• posttranslational modification
• signal transduction
• single nucleotide polymorphism

• Binding sites
• Esophageal squamous cell carcinoma
• Genetic susceptibility
• Single nucleotide polymorphism
• miR-17-92 cluster

Metastasis is one of the characteristics of advanced cancer and the primary cause of cancer-related deaths from cancer, but the mechanism underlying metastasis is unclear, and there is a lack of metastasis markers. PTPRT is a protein-coding gene involved in both signal transduction and cellular adhesion. It is also known as a tumor suppressor gene that inhibits cell malignant proliferation by inhibiting the STAT3 pathway. Recent studies have reported that PTPRT is involved in the early metastatic seeding of colorectal cancer; however, the correlation between PTPRT and metastasis in other types of cancer has not been revealed. A combined analysis using a dataset from the genomics evidence neoplasia information exchange (GENIE) and cBioPortal revealed that PTPRT mutation is associated with poor prognosis in pan-cancer and non-small-cell lung cancer. The mutations of PTPRT or “gene modules” containing PTPRT are significantly enriched in patients with metastatic cancer in multiple cancers, suggesting that the PTPRT mutations serve as potential biomarkers of cancer metastasis.

• acute myeloid leukaemia
• cancer genetics
• apoptosis
• oncogenes

• Animals
• Carcinogenesis/genetics
• Cell Line, Tumor
• Epigenesis, Genetic
• Gene Expression Regulation, Leukemic
• Humans
• Leukemia, Myeloid, Acute/genetics
• Mice, Inbred C57BL
• Mice, Knockout
• MicroRNAs/genetics
• Myeloid-Lymphoid Leukemia Protein/genetics
• Oncogene Proteins, Fusion/genetics
• RNA Polymerase II/genetics
• Mice

• KWF Kankerbestrijding (Dutch Cancer Society)
• Dutch Research Council (NWO) Medium Investment Grant 91116004 (partly financed by ZonMw)

Esophageal squamous cell carcinoma (ESCC) is the major subtype of esophageal cancer that is prevalent in Eastern Asia. Despite recent advances in therapy, the outcome of ESCC patients is still dismal. MicroRNAs (miRNAs) are non-coding RNAs which can negatively modulate gene expression at the post-transcriptional level. The involvement and roles of miRNAs have become one of the hot topics of cancer research in recent years. In ESCC, genetic variations within miRNA coding genes were found to have distinct epidemiological significance in different populations. Dysregulated expression of several miRNAs was reported to be associated with therapeutic response. Functionally, miRNAs can act either in an oncogenic or a tumor-suppressive manner during tumorigenesis of ESCC by interrupting signaling pathways associated with cell proliferation, metabolism, cancer stemness, and resistance to chemo- or radiotherapy. Moreover, miRNAs modulate metastasis of ESCC by targeting genes that regulate cytoskeleton dynamics, extracellular matrix remodeling, epithelial-mesenchymal transition, and tumor microenvironment. Most importantly, mounting evidence suggests that inhibiting oncogenic miRNAs or restoring the loss of tumor-suppressive miRNAs has therapeutic potential in the treatment of ESCC. Here, we review and discuss recent studies on the significance, biological functions, and therapeutic potential of miRNAs in tumorigenesis and metastasis of ESCC.

• MicroRNAs
• Dysregulation
• Tumorigenesis
• Metastasis
• Therapeutic potential
• Esophageal squamous cell carcinoma

• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Biomarkers, Tumor/genetics
• Breast Neoplasms/drug therapy
• Breast Neoplasms/genetics
• Breast Neoplasms/pathology
• DNA Methylation
• Databases, Genetic
• Drug Resistance, Neoplasm
• Female
• Humans
• Middle Aged
• Neoplasm Grading
• Neoplasm Staging
• Prognosis
• Promoter Regions, Genetic
• Receptor-Like Protein Tyrosine Phosphatases, Class 2/genetics
• Survival Analysis
• Up-Regulation
• Young Adult

Although microRNAs (miRNAs)-based cancer therapy strategies have been proved to be efficient and superior to chemotherapeutic agents in certain extent, the unstable properties of miRNAs significantly impaired the wide application. Therefore, how to safely deliver the miRNAs to the targeted site of action is the most pivotal step to achieve the ideal treatment effect. In the present work, the miR-128-3p, which is able of inducing chromosomal instability, was loaded into the nanocomplexes developed by the PEG-PDMAEMA (PDMAEMA-NP). By this way, the miR-128-3p was shielded from exposure to various degrading enzymes in bloodstream. Additionally, the PEGylation endowed the PDMAEMA-NP with long time of circulation as demonstrated in vivo by pharmacokinetics investigation. To target and deliver the miR-128-3p to the site of action, a tumor-homing peptide CPKSNNGVC, which specifically targets the monocarboxylate transporter 1 (MCT1), was decorated on the surface of PDMAEMA-NP. Both in vitro and in vivo experiments demonstrated that more efficient delivery of miR-128-3p to cells or tumor tissues was obtained by the PDMAEMA-NP than plasmid. Additionally, modification of C peptides further enhanced the tumor accumulation of miR-128-3p, and in turn contributed to the stronger tumor growth inhibition effect. Underlying mechanisms study revealed that the miR-128-3p inhibited the growth, migration, and invasion of colorectal cancer (CRC) cells and progress of CRC tissues through silence of the activity of PI3K/AKT and MEK/ERK pathway. By this way, the chemotherapy effect of 5-Fluorouracil (5-Fu) was dramatically improved after co-treating the cells with miR-128-3p formulations.

• 5-Fluorouracil
• MicroRNAs
• nanocomplexes
• signaling pathways
• tumor-targeting

CD133 is one of the important cancer stem cells (CSCs) markers of hepatocellular carcinoma (HCC). The aim of this study was to explore the relationship between CD133 single-nucleotide polymorphisms (SNPs) and risk factors associated with HCC susceptibility and clinicopathological features in HCC cases and healthy controls from the Guangxi region of southern China.

A case control study was conducted, including 565 HCC patients and 561 control subjects. The genotyping of rs2240688 was performed using the SNaPshot method. Unconditional logistic regression was used to correct for gender, age, and other confounding factors. Odds ratio (OR) and its 95% confidence interval (CI) were calculated to analyze the relationship between allele and genotype frequency and the risk of HCC.

The distribution frequencies of CD133 alleles and genotypes in the HCC case group and the control group were statistically significant (P<0.05). The CA heterozygous (P=0.003, OR =1.463, 95% CI: 1.134–1.887) and CC homozygous genotypes (P=0.036, OR =1.910, 95% CI: 1.044–3.493), as well as C carrier status (P=0.004, OR =1.465, 95% CI: 1.136–1.889) and C alleles (P=0.004, OR =1.465, 95% CI: 1.136–1.889), were associated with an increased risk of HCC. Additionally, in the subgroup analysis of CD133 rs2240688 polymorphism and clinical characteristics, the results showed that the genotype distribution of CD133 rs2240688 was significantly different in genotype distribution of metastasis and alanine aminotransferase (ALT).

the expression of miRNA binding site rs2240688 of tumor stem cell marker gene CD133 in HCC may be a promising marker for the prediction of HCC, but larger studies are still needed.

• CD133
• Hepatocellular carcinoma (HCC)
• cancer stem cells (CSCs)
• rs2240688
• single-nucleotide polymorphisms (SNPs)

Esophageal cancer (EC) is the eighth most common and sixth leading cause of cancer-related mortality in the world. Despite breakthroughs in EC diagnosis and treatment, patients with complete pathologic response after being submitted to chemoradiotherapy are still submitted to surgery, despite its high morbidity. Single-nucleotide polymorphisms (SNPs) in miRNA, miRNA-binding sites, and in its biogenesis pathway genes can alter miRNA expression patterns, thereby influencing cancer risk and prognosis. In this review, we systematized the information available regarding the impact of these miR-SNPs in EC development and prognosis. We found 34 miR-SNPs that were associated with EC risk. Despite the promising applicability of these miR-SNPs as disease biomarkers, they still lack validation in non-Asian populations. Moreover, there should be more pathway-based approaches to evaluate the cumulative effect of multiple unfavorable genotypes and, consequently, identify miR-SNPs signatures capable of predicting EC therapy response and prognosis.

• esophageal cancer
• miR-SNPs
• molecular biomarkers

Growth differentiation factor 15 (GDF15) is a strong predictor of cardiovascular events and mortality in individuals with or without cardiovascular diseases. Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) target sites, also known as miRSNPs, are known to enhance or weaken miRNA-mRNA interactions and have been linked to diseases such as cardiovascular disease and cancer. In this study, we aimed to elucidate the functional significance of the miRSNP rs1054564 in regulating GDF15 levels. Two rs1054564-containing binding sites for hsa-miR-873-5p and hsa-miR-1233-3p were identified in the 3′ untranslated region (UTR) of the GDF15 transcript using bioinformatics tools. Their activities were further characterized by in vitro reporter assays. Bioinformatics prediction suggested that miRNA binding sites harboring the rs1054564-G allele had lower free energies than those with the C allele and therefore were better targets with higher affinities for both hsa-miR-873-5p and hsa-miR-1233-3p. Reporter assays showed that luciferase activity was significantly decreased by rs1054564-G-containing 3′ UTRs for both miRNAs (P < 0.05) and was restored by miRNA inhibitors. Comparing the fold suppression of the two miRNAs, only that of hsa-miR-1233-3p showed significant changes between the rs1054564-G- and C-containing 3′ UTRs (P = 0.034). In addition, western blots showed that transfection of both miRNA mimics significantly decreased endogenous GDF15 expression in a melanoma cell line (P < 0.05). Taken together, our findings demonstrate that GDF15 is a target of hsa-miR-873-5p and hsa-miR-1233-3p and that the rs1054564-C allele partially abolishes hsa-miR-1233-3p-mediated translational suppression of GDF15. These results suggest that rs1054564 confers allele-specific translational repression of GDF15 via hsa-miR-1233-3p. Our work thus provides biological insight into the previously reported clinical association between rs1054564 and plasma GDF15 levels.

• 3' Untranslated Regions/genetics
• Alleles
• Base Sequence
• Binding Sites/genetics
• Cell Line, Tumor
• Computer Simulation
• Growth Differentiation Factor 15/genetics
• Growth Differentiation Factor 15/metabolism
• HEK293 Cells
• Humans
• MicroRNAs/chemistry
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Nucleic Acid Conformation
• Polymorphism, Single Nucleotide/genetics
• Protein Biosynthesis/genetics