Min Niu

Bio: Min Niu is an academic researcher from Shanxi Medical University. The author has contributed to research in topics: Fascin & Medicine. The author has an hindex of 8, co-authored 20 publications receiving 226 citations.

circPARD3 drives malignant progression and chemoresistance of laryngeal squamous cell carcinoma by inhibiting autophagy through the PRKCI-Akt-mTOR pathway

Abstract: Laryngeal squamous cell carcinoma (LSCC) is the second most common malignant tumor in head and neck. Autophagy and circular RNAs (circRNAs) play critical roles in cancer progression and chemoresistance. However, the function and mechanism of circRNA in autophagy regulation of LSCC remain unclear. The autophagy-suppressive circRNA circPARD3 was identified via RNA sequencing of 107 LSCC tissues and paired adjacent normal mucosal (ANM) tissues and high-content screening. RT-PCR, Sanger sequencing, qPCR and fluorescence in situ hybridization were performed to detect circPARD3 expression and subcellular localization. Biological functions of circPARD3 were assessed by proliferation, migration, invasion, autophagic flux, and chemoresistance assays using in vitro and in vivo models. The mechanism of circPARD3 was investigated by RNA immunoprecipitation, RNA pulldown, luciferase reporter assays, western blotting and immunohistochemical staining. Autophagy was inhibited in LSCC, and circPARD3 was upregulated in the LSCC tissues (n = 100, p < 0.001). High circPARD3 level was associated with advanced T stages (p < 0.05), N stages (p = 0.001), clinical stages (p < 0.001), poor differentiation degree (p = 0.025), and poor prognosis (p = 0.002) of LSCC patients (n = 100). Functionally, circPARD3 inhibited autophagy and promoted LSCC cell proliferation, migration, invasion and chemoresistance. We further revealed that activation of the PRKCI-Akt-mTOR pathway through sponging miR-145-5p was the main mechanism of circPARD3 inhibited autophagy, promoting LSCC progression and chemoresistance. Our study reveals that the novel autophagy-suppressive circPARD3 promotes LSCC progression and chemoresistance through the PRKCI-Akt-mTOR pathway, providing new insights into circRNA-mediated autophagy regulation and potential biomarker and target for LSCC treatment.

Circular RNA circCORO1C promotes laryngeal squamous cell carcinoma progression by modulating the let-7c-5p/PBX3 axis

Abstract: Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the head and neck. LSCC patients have seriously impaired vocal, respiratory, and swallowing functions with poor prognosis. Circular RNA (circRNA) has attracted great attention in cancer research. However, the expression patterns and roles of circRNAs in LSCC remain largely unknown. RNA sequencing was performed on 57 pairs of LSCC and matched adjacent normal mucosa tissues to construct circRNA, miRNA, and mRNA expression profiles. RT-PCR, qPCR, Sanger sequencing, and FISH were undertaken to study the expression, localization, and clinical significance of circCORO1C in LSCC tissues and cells. The functions of circCORO1C in LSCC were investigated by RNAi-mediated knockdown, proliferation analysis, EdU staining, colony formation assay, Transwell assay, and apoptosis analysis. The regulatory mechanisms among circCORO1C, let-7c-5p, and PBX3 were investigated by luciferase assay, RNA immunoprecipitation, western blotting, and immunohistochemistry. circCORO1C was highly expressed in LSCC tissues and cells, and this high expression was closely associated with the malignant progression and poor prognosis of LSCC. Knockdown of circCORO1C inhibited the proliferation, migration, invasion, and in vivo tumorigenesis of LSCC cells. Mechanistic studies revealed that circCORO1C competitively bound to let-7c-5p and prevented it from decreasing the level of PBX3, which promoted the epithelial–mesenchymal transition and finally facilitated the malignant progression of LSCC. circCORO1C has an oncogenic role in LSCC progression and may serve as a novel target for LSCC therapy. circCORO1C expression has the potential to serve as a novel diagnostic and prognostic biomarker for LSCC detection.

Whole-Transcriptome Analysis of CD133+CD144+ Cancer Stem Cells Derived from Human Laryngeal Squamous Cell Carcinoma Cells

Abstract: Background/Aims: CD133+CD44+ cancer stem cells previously isolated from laryngeal squamous cell carcinoma (LSCC) cell lines showed strong malignancy and tumorigenicity. However, the molecular mechanism underlying the enhanced malignancy remained unclear. Methods: Cell proliferation assay, spheroid-formation experiment, RNA sequencing (RNA-seq), miRNA-seq, bioinformatic analysis, quantitative real-time PCR, migration assay, invasion assay, and luciferase reporter assay were used to identify differentially expressed mRNAs, lncRNAs, circRNAs and miRNAs, construct transcription regulatory network, and investigate functional roles and mechanism of circRNA in CD133+CD44+ laryngeal cancer stem cells. Results: Differentially expressed genes in TDP cells were mainly enriched in the biological processes of cell differentiation, regulation of autophagy, negative regulation of cell death, regulation of cell growth, response to hypoxia, telomere maintenance, cellular response to gamma radiation, and regulation of apoptotic signaling, which are closely related to the malignant features of tumor cells. We constructed the regulatory network of differentially expressed circRNAs, miRNAs and mRNAs. qPCR findings for the expression of key genes in the network were consistent with the sequencing data. Moreover, our data revealed that circRNA hg19_circ_0005033 promotes proliferation, migration, invasion, and chemotherapy resistance of laryngeal cancer stem cells. Conclusions: This study provides potential biomarkers and targets for LSCC diagnosis and therapy, and provide important evidences for the heterogeneity of LSCC cells at the transcription level.

miR-424-5p Promotes Proliferation, Migration and Invasion of Laryngeal Squamous Cell Carcinoma.

Abstract: Background Recent studies revealed that miR-424-5p regulates the malignant behavior of multiple cancer types. However, the expression and function of miR-424-5p in laryngeal squamous cell carcinoma (LSCC) is unclear. Purpose This study aimed to evaluate the association of miR-424-5p level with clinical features of LSCC and investigate the effect and potential mechanism of miR-424-5p on LSCC progression. Methods The expression of miR-424-5p in LSCC and paired adjacent normal margin (ANM) tissues from 106 patients with LSCC were analyzed by quantitative PCR (qPCR), and clinical significance was analyzed. Target genes of miR-424-5p were predicted, followed by functional annotation. The functional role of miR-424-5p in LSCC was investigated by molecular and cellular experiments with LSCC cell lines, with flow cytometry used for cell cycle analysis. In addition, miR-424-5p regulation of the predicted target gene cell adhesion molecule 1 (CADM1) was validated by qPCR, Western blot analysis and luciferase reporter assay. Results miR-424-5p was upregulated in LSCC versus ANM tissues. High miR-424-5p level was significantly associated with poor differentiation, advanced tumor stage and cervical lymph node metastasis. Bioinformatics analysis showed that miR-424-5p target genes are mainly enriched in biological processes of the cell cycle, cell division, and negative regulation of cell migration, and were involved in multiple cancer-related pathways. Overexpression of miR-424-5p promoted proliferation, migration, invasion, and adhesion of LSCC cells and affected the cell cycle progression. Additionally, CADM1 was a direct target of miR-424-5p in LSCC cells. Conclusion miR-424-5p functions as an oncogene to promote the aggressive progression of LSCC, and CADM1 is a direct downstream target of miR-424-5p in LSCC cells. miR-424-5p may be a potential therapeutic target in LSCC.

MicroRNAs: Target Recognition and Regulatory Functions

Abstract: MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

Circular RNAs in Cancer: emerging functions in hallmarks, stemness, resistance and roles as potential biomarkers

Abstract: Circular RNAs (circRNAs) are a class of RNA molecules with closed loops and high stability. CircRNAs are abundantly expressed in eukaryotic organisms and exhibit both location- and step-specificity. In recent years, circRNAs are attracting considerable research attention attributed to their possible contributions to gene regulation through a variety of actions, including sponging microRNAs, interacting with RNA-binding proteins, regulating transcription and splicing, and protein translation. Growing evidence has revealed that circRNAs play critical roles in the development and progression of diseases, especially in cancers. Without doubt, expanding our understanding of circRNAs will enrich knowledge of cancer and provide new opportunities for cancer therapy. In this review, we provide an overview of the characteristics, functions and functional mechanisms of circRNAs. In particular, we summarize current knowledge regarding the functions of circRNAs in the hallmarks, stemness, resistance of cancer, as well as the possibility of circRNAs as biomarkers in cancer.

Systematic Localization of Common Disease-Associated Variation in

Abstract: ): Genome-wide association studies have identified many noncoding variants associated with common diseases and traits. We show that these variants are concentrated in regulatory DNA marked by deoxyribonuclease I (DNase I) hypersensitive sites (DHSs). Eighty-eight percent of such DHSs are active during fetal development and are enriched in variants associated with gestational exposure–related phenotypes. We identified distant gene targets for hundreds of variant-containing DHSs that may explain phenotype associations. Disease-associated variants systematically perturb transcription factor recognition sequences, frequently alter allelic chromatin states, and form regulatory networks. We also demonstrated tissue-selective enrichment of more weakly disease-associated variants within DHSs and the de novo identification of pathogenic cell types for Crohn’s disease, multiple sclerosis, and an electrocardiogram trait, without prior knowledge of physiological mechanisms. Our results suggest pervasive involvement of regulatory DNA variation in common human disease and provide pathogenic insights into diverse disorders.

Biological Roles and Mechanisms of Circular RNA in Human Cancers.

Abstract: Circular RNA (circRNA) is an intriguing class of RNA with covalently closed-loop structure and is highly stable and conservative. As new members of the ncRNAs, the function, mechanism, potential diagnostic biomarker, and therapeutic target have raised increased attention. Most circRNAs are presented with characteristics of abundance, stability, conservatism, and often exhibiting tissue/developmental-stage-specific manner. Over 30,000 circRNAs have been identified with their unique structures to maintain stability more easily than linear RNAs. An increased numbers of circRNAs are dysregulated and involved in several biological processes of malignance, such as tumorigenesis, growth, invasion, metastasis, apoptosis, and vascularization. Emerging evidence suggests that circRNAs play important roles by acting as miRNA sponge or protein scaffolding, autophagy regulators, and interacting with RNA-binding protein (RBP), which may potentially serve as a novel promising biomarker for prevention, diagnosis and therapeutic target for treatment of human cancer with great significance either in scientific research or clinic arena. This review introduces concept, major features of circRNAs, and mainly describes the major biological functions and clinical relevance of circRNAs, as well as expressions and regulatory mechanisms in various types of human cancer, including pathogenesis, mode of action, potential target, signaling regulatory pathways, drug resistance, and therapeutic biomarkers. All of which provide evidence for the potential utilities of circRNAs in the diagnosis and treatment of cancer.