microRNAs have received wide attention as potential therapeutic targets. This study explored the action of miR-128-3p in acute myeloid leukemia (AML). miR-128-3p expression in AML was determined by quantitative PCR method. MTT proliferation assay and immunoblot assay were employed to detect proteins related to proliferation and apoptosis in THP-1 cells overexpressing miR-128-3p. RNA immunoprecipitation and dual luciferase reporting system were utilized to verify downstream targets of miR-128-3p. Flow cytometry was conducted to analyze the apoptosis rate and immune escape of THP-1 cells in the T-cell co-culture system. miR-128-3p was lowly expressed in AML patients (reduced by 41.6%). Overexpression of miR-128-3p inhibited THP-1 cell proliferation and immune escape, and stimulated apoptosis. ZEB1 was a downstream target of miR-128-3p, and up-regulation of miR-128-3p inhibited ZEB1 mRNA and protein expression (respectively reduced by 65.8% and 42.0%). Upregulating ZEB1 reversed the inhibitory effect of upregulating miR-128-3p on THP-1 cell proliferation and immune escape. Upregulating ZEB1 promoted PD-L1 protein expression (increased by 0.75-fold). Blocking PD-L1 reversed the promotion of THP-1 cell proliferation and immune escape by upregulating ZEB1. The miR-128-3p/ZEB1/PD-L1 axis is involved in regulating the proliferation and immune escape of AML cells, providing new insights into the molecular mechanism of miR-128-3p in AML and, more importantly, a new target for immunotherapy of AML.

Cervical cancer (CC) stem cell-like cells (CCSLCs), defined by the capacity of differentiation and self-renewal and proliferation, play a significant role in the progression of CC. However, the molecular mechanisms regulating their self-renewal are poorly understood. Therefore, elucidation of the epigenetic mechanisms that drive cancer stem cell self-renewal will enhance our ability to improve the effectiveness of targeted therapies for cancer stem cells.

To explore how DNA methyltransferase 1 (DNMT1)/miR-342-3p/Forkhead box M1 (FoxM1), which have been shown to have abnormal expression in CCSLCs, and their signaling pathways could stimulate self-renewal-related stemness in CCSLCs.

Sphere-forming cells derived from CC cell lines HeLa, SiHa and CaSki served as CCSLCs. Self-renewal-related stemness was identified by determining sphere and colony formation efficiency, CD133 and CD49f protein level, and SRY-box transcription factor 2 and octamer-binding transcription factor 4 mRNA level. The microRNA expression profiles between HeLa cells and HeLa-derived CCSLCs or mRNA expression profiles that HeLa-derived CCSLCs were transfected with or without miR-342-3p mimic were compared using quantitative PCR analysis. The expression levels of DNMT1 mRNA, miR-342-3p, and FoxM1 protein were examined by quantitative real-time PCR and western blotting. In vivo carcinogenicity was assessed using a mouse xenograft model. The functional effects of the DNMT1/miR-342-3p/FoxM1 axis were examined by in vivo and in vitro gain-of-activity and loss-of-activity assessments. Interplay among DNMT1, miR-342-3p, and FoxM1 was tested by methylation-specific PCR and a respective luciferase reporter assay.

CCSLCs derived from the established HeLa cell lines displayed higher self-renewal-related stemness, including enhanced sphere and colony formation efficiency, increased CD133 and CD49f protein level, and heightened transcriptional quantity of stemness-related factors SRY-box transcription factor 2 and octamer-binding transcription factor 4 in vitro as well as a stronger tumorigenic potential in vivo compared to their parental cells. Moreover, quantitative PCR showed that the miR-342-3p level was downregulated in HeLa-derived CCSLCs compared to HeLa cells. Its mimic significantly decreased DNMT1 and FoxM1 mRNA expression levels in CCSLCs. Knockdown of DNMT1 or miR-342-3p mimic transfection suppressed DNMT1 expression, increased miR-342-3p quantity by promoter demethylation, and inhibited CCSLC self-renewal. Inhibition of FoxM1 by shRNA transfection also resulted in the attenuation of CCSLC self-renewal but had little effect on the DNMT1 activity and miR-342-3p expression. Furthermore, the loss of CCSLC self-renewal exerted by miR-342-3p mimic was inverted by the overexpression of DNMT1 or FoxM1. Furthermore, DNMT1 and FoxM1 were recognized as straight targets by miR-342-3p in HeLa-derived CCSLCs.

Our findings suggested that a novel DNMT1/miR-342-3p/FoxM1 signal axis promotes CCSLC self-renewal and presented a potential target for the treatment of CC through suppression of CCSLC self-renewal. However, this pathway has been previously implicated in CC, as evidenced by prior studies showing miR-342-3p-mediated downregulation of FoxM1 in cervical cancer cells. Additionally, research on liver cancer further supports the involvement of miR-342-3p in suppressing FoxM1 expression. While our study contributed to this body of knowledge, we did not present a completely novel axis but reinforced the therapeutic potential of targeting the DNMT1/miR-342-3p/FoxM1 axis to suppress CCSLC self-renewal in CC treatment.

Ataxia telangiectasia (AT) is a rare disorder characterized by neurodegeneration, combined immunodeficiency, a predisposition to malignancies, and high clinical variability. Profiling of microRNAs (miRNAs) may offer insights into the underlying mechanisms of complex rare human diseases, as miRNAs play a role in various biological functions including proliferation, differentiation, and DNA repair. In this study, we investigate the differential expression of miRNAs in samples from AT patients to identify miRNA patterns and analyze how these patterns are related to the disease.

We enrolled 20 AT patients (mean age 17.7 ± 9.6 years old) and collected clinical and genetic data. We performed short non-coding RNA-seq analysis on peripheral blood mononuclear cells (PBMCs) and fibroblasts to compare the miRNA expression profile between AT patients and controls.

We observed 42 differentially expressed (DE)-miRNAs in blood samples and 26 in fibroblast samples. Among these, three DE-miRNAs, miR-342-3p, miR-30a-5p, and miR-195-5p, were further validated in additional AT samples, confirming their dysregulation.

We identified an AT-related miRNA signature in blood cells and fibroblast samples collected from a group of AT patients. We also predicted several dysregulated pathways, primarily related to cancer, immune system control, or inflammatory processes. The findings suggest that miRNAs may provide insights into the pathophysiology and tumorigenesis of AT and have the potential to serve as useful biomarkers in cancer research.

Acute myeloid leukemia (AML) is a genetically extremely heterogeneous disease. Drug resistance after induction therapy is a very frequent event resulting in poor medium survival times. Therefore, the identification of new targets and treatment modalities is a medical high priority issue. We addressed our attention to circular RNAs (circRNAs), which can act as oncogenes or tumor suppressors in AML. We searched the literature (PubMed) and identified eight up-regulated and two down-regulated circ-RNAs with activity in preclinical in vivo models. In addition, we identified twenty-two up-regulated and four down-regulated circRNAs with activity in preclinical in vitro systems, but pending in vivo activity. Up-regulated RNAs are potential targets for si- or shRNA-based approaches, and down-regulated circRNAs can be reconstituted by replacement therapy to achieve a therapeutic benefit in preclinical systems. The up-regulated targets can be tackled with small molecules, antibody-based entities, or other modes of intervention. For down-regulated targets, up-regulators must be identified. The ranking of the identified circRNAs with respect to therapy of AML will depend on further target validation experiments.