Advances in the functional roles of N6-methyladenosine modification in cancer progression: mechanisms and clinical implications

2022 ◽  
Author(s):  
Peilin Chen ◽  
Jianhang Hu ◽  
Xiaodong Han ◽  
Yabing Chen
Keyword(s):  
Cancer Progression ◽  
Clinical Implications ◽  
Functional Roles

scholarly journals Recent Advances in Nanotechnology with Nano-Phytochemicals: Molecular Mechanisms and Clinical Implications in Cancer Progression

2021 ◽  
Vol 22 (7) ◽  
pp. 3571
Author(s):  
Bonglee Kim ◽  
Ji-Eon Park ◽  
Eunji Im ◽  
Yongmin Cho ◽  
Jinjoo Lee ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Future Research ◽  
Clinical Implications ◽  
Research Perspectives ◽  
Current Review ◽  
Gold Silver ◽  
Significant Efficacy ◽  
Rapid Clearance

Biocompatible nanoparticles (NPs) containing polymers, lipids (liposomes and micelles), dendrimers, ferritin, carbon nanotubes, quantum dots, ceramic, magnetic materials, and gold/silver have contributed to imaging diagnosis and targeted cancer therapy. However, only some NP drugs, including Doxil® (liposome-encapsulated doxorubicin), Abraxane® (albumin-bound paclitaxel), and Oncaspar® (PEG-Asparaginase), have emerged on the pharmaceutical market to date. By contrast, several phytochemicals that were found to be effective in cultured cancer cells and animal studies have not shown significant efficacy in humans due to poor bioavailability and absorption, rapid clearance, resistance, and toxicity. Research to overcome these drawbacks by using phytochemical NPs remains in the early stages of clinical translation. Thus, in the current review, we discuss the progress in nanotechnology, research milestones, the molecular mechanisms of phytochemicals encapsulated in NPs, and clinical implications. Several challenges that must be overcome and future research perspectives are also described.

scholarly journals Exosomal S100A4 derived from highly metastatic hepatocellular carcinoma cells promotes metastasis by activating STAT3

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Haoting Sun ◽  
Chaoqun Wang ◽  
Beiyuan Hu ◽  
Xiaomei Gao ◽  
Tiantian Zou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Calcium Binding ◽  
Tumor Metastasis ◽  
Metastatic Potential ◽  
Functional Roles ◽  
Stat3 Phosphorylation ◽  
Hcc Cells

AbstractIntercellular cross-talk plays important roles in cancer progression and metastasis. Yet how these cancer cells interact with each other is still largely unknown. Exosomes released by tumor cells have been proved to be effective cell-to-cell signal mediators. We explored the functional roles of exosomes in metastasis and the potential prognostic values for hepatocellular carcinoma (HCC). Exosomes were extracted from HCC cells of different metastatic potentials. The metastatic effects of exosomes derived from highly metastatic HCC cells (HMH) were evaluated both in vitro and in vivo. Exosomal proteins were identified with iTRAQ mass spectrum and verified in cell lines, xenograft tumor samples, and functional analyses. Exosomes released by HMH significantly enhanced the in vitro invasion and in vivo metastasis of low metastatic HCC cells (LMH). S100 calcium-binding protein A4 (S100A4) was identified as a functional factor in exosomes derived from HMH. S100A4rich exosomes significantly promoted tumor metastasis both in vitro and in vivo compared with S100A4low exosomes or controls. Moreover, exosomal S100A4 could induce expression of osteopontin (OPN), along with other tumor metastasis/stemness-related genes. Exosomal S100A4 activated OPN transcription via STAT3 phosphorylation. HCC patients with high exosomal S100A4 in plasma also had a poorer prognosis. In conclusion, exosomes from HMH could promote the metastatic potential of LMH, and exosomal S100A4 is a key enhancer for HCC metastasis, activating STAT3 phosphorylation and up-regulating OPN expression. This suggested exosomal S100A4 to be a novel prognostic marker and therapeutic target for HCC metastasis.

scholarly journals Functional roles of sialylation in breast cancer progression through miR-26a/26b targeting ST8SIA4

2016 ◽  
Vol 7 (12) ◽  
pp. e2561-e2561 ◽  
Author(s):  
Xiaolu Ma ◽  
Weijie Dong ◽  
Zhen Su ◽  
Lifen Zhao ◽  
Yuan Miao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Breast Cancer Progression ◽  
Functional Roles

Molecular characterization of pancreatic cancers as seen in the SLUG gene revealing cancer progression.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 433-433 ◽  
Author(s):  
Natsuko Kawanishi ◽  
Yasmine Baca ◽  
Joanne Xiu ◽  
Hiroyuki Arai ◽  
Jingyan Wang ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Immune Cell ◽  
Pancreatic Tumors ◽  
Therapeutic Effects ◽  
Expression Levels ◽  
Functional Roles ◽  
Genome Medicine ◽  
Whole Transcriptome Sequencing ◽  
Slug Expression ◽  
Tumor Mutational Burden

433 Background: The SLUG gene plays an important role in EMT by repressing E-cadherin and promotes metastasis. Previous data suggest that overexpressed SLUG gene in pancreatic cancer (PC) showing a high frequency of metastasis and poor prognosis. As SLUG contribution to characteristics or metastatic features remains elusive, we clarified its functional roles in PC progression. Methods: A total of 2958 pancreatic tumors were analyzed using Whole Transcriptome sequencing, NextGen Sequencing (NGS) (NextSeq, 592 gene panel) or Whole Exome Sequencing (WES) (NovaSeq) (Caris Life Sciences, Phoenix, AZ). Microsatellite instability (MSI) status was tested by fragment analysis, immunohistochemistry (IHC) and NGS. PD-L1 expression was tested by IHC. Tumor mutational burden (TMB) was measured by counting all mutations found per tumor (a universal cutoff point of ≧10 mutations per MB). Immune cell fraction was calculated by quanTIseq (Finotello 2019, Genome Medicine). Results: A total of 1274 primary and 1684 metastatic pancreatic tumors were included for this study. They were divided equally into four classes in each group, according to their SLUG expression levels. Tumors in the highest quartile of SLUG expression (QH) showed significantly higher frequency in peritoneal-retroperitoneal-omentum metastasis (15.0%) compared to the lowest quartile (QL) (4.8%) (p = .0001). Similar trends were seen in the abdomen (6% vs 1%, p = .001) and bone (2.8% vs 0.0%, p = .005). However, liver (55.0% in QH vs 63.1% in QL) and lung (2.8% vs 14.1%) metastasis occurred most frequently in QL and the least frequently in QH (p = .0197 and p = .001, respectively). This data indicated that tumors with high SLUG gene expression levels tend to lead to disseminated metastasis, and with low expression levels, they tend to spread intravascularly. We detected significant differences among genetic mutations in ATM (5.7% in QL vs 1.8% in QH, p < 0.001) and APC (2.9% vs 0.5%, p < 0.001), and Wnt signaling expressions were higher in QL (4.6%) than QH (0.7%) (p < 0.001). Binary TMB-H and MSI-H tumors had higher frequencies in QL (2.7% and 2.1%) compared to QH (0.3% and 0.1%) (p < 0.001 in both). Contrastingly, PD-L1 expression levels were higher in QH (23.4%) compared to QL (11.0%) (p < 0.001) and had a linear relationship with the expression levels. The median values of the population of B cells, M1 and M2 macrophages were significantly higher in QH compared to QL, but those of myeloid dendritic and CD8+T cells conversely decrease as the SLUG expression increases. Conclusions: Our data indicated the SLUG expression level could determine the tumor characteristics in progression, especially the pattern of metastasis in PC, and it could possibly predict the prognosis and/or therapeutic effects. We also showed immune oncologic markers which have some relationships with SLUG expressions. Further investigation is warranted to better understand SLUG gene functions.

scholarly journals Functional roles of antisense enhancer RNA for promoting prostate cancer progression

Theranostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1780-1794
Author(s):  
Chun-Wu Pan ◽  
Simeng Wen ◽  
Lei Chen ◽  
Yulei Wei ◽  
Yuanjie Niu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Prostate Cancer Progression ◽  
Functional Roles ◽  
Enhancer Rna

Long non-coding RNAs in prostate cancer: Functional roles and clinical implications

2019 ◽  
Vol 464 ◽  
pp. 37-55 ◽  
Author(s):  
Yun-Hua Xu ◽  
Jun-Li Deng ◽  
Guo Wang ◽  
Yuan-Shan Zhu
Keyword(s):  
Prostate Cancer ◽  
Clinical Implications ◽  
Functional Roles ◽  
Non Coding Rnas

scholarly journals CircCDR1as upregulates autophagy under hypoxia to promote tumor cell survival via AKT/ERK½/mTOR signaling pathways in oral squamous cell carcinomas

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Ling Gao ◽  
Zhi-Chao Dou ◽  
Wen-Hao Ren ◽  
Shao-Ming Li ◽  
Xiao Liang ◽  
...  
Keyword(s):  
Cell Survival ◽  
Cancer Progression ◽  
Squamous Cell ◽  
Degradation Mechanism ◽  
Cell Metabolism ◽  
Mice Model ◽  
Functional Roles ◽  
Promote Tumor Cell

Abstract Autophagy, as an important non-selective degradation mechanism, could promote tumor initiation and progression by maintaining cellular homeostasis and the cell metabolism as well as cell viability. CircCDR1as has been shown to function as an oncogene in cancer progression, however, it remains largely unknown as to how autophagy is regulated by circCDR1as in oral squamous cell carcinoma (OSCC). In this study, we validated the functional roles of circCDR1as in regulation of autophagy in OSCC cells and further investigated how circCDR1as contributed to cell survival via up-regulating autophagy under a hypoxic microenvironment by using combination of human tissue model, in vitro cell experiments and in vivo mice model. We found that hypoxia promoted the expression level of circCDR1as in OSCC cells and elevated autophagy. In addition, circCDR1as further increased hypoxia-mediated autophagy by targeting multiple key regulators of autophagy. We revealed that circCDR1as enhanced autophagy in OSCC cells via inhibition of rapamycin (mTOR) activity and upregulation of AKT and ERK½ pathways. Overexpression of circCDR1as enhanced OSCC cells viability, endoplasmic reticulum (ER) stress, and inhibited cell apoptosis under a hypoxic microenvironment. Moreover, circCDR1as promoted autophagy in OSCC cells by sponging miR-671-5p. Collectively, these results revealed that high expression of circCDR1as enhanced the viability of OSCC cells under a hypoxic microenvironment by promoting autophagy, suggesting a novel treatment strategy involving circCDR1as and the inhibition of autophagy in OSCC cells.

scholarly journals A Double-Negative Feedback Interaction between MicroRNA-29b and DNMT3A/3B Contributes to Ovarian Cancer Progression

2016 ◽  
Vol 39 (6) ◽  
pp. 2341-2352 ◽  
Author(s):  
Yue Teng ◽  
Xiaohang Zuo ◽  
Meng Hou ◽  
Yan Zhang ◽  
Chen Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Negative Feedback ◽  
Cpg Island ◽  
Immunohistochemical Analysis ◽  
Binding Activity ◽  
Luciferase Reporter ◽  
Double Negative ◽  
Functional Roles ◽  
Direct Binding

Background: Epigenetic abnormalities are increasingly observed in multiple malignancies, including epithelial ovarian cancer (EOC), and their effects can be significantly counteracted by tumor-suppressor microRNAs, namely epi-miRNAs. Here, we investigated the role of miR-29b, a well-established epi-miRNA, in the DNA methylation regulation of EOC cells. Methods: The correlation between miR-29b and DNMT3A/3B expression was evaluated by RT-qPCR, western blotting and immunohistochemical analysis. The functional roles of miR-29b and DNMT3A/3B were tested by anti-miRs and microRNA precursors. A luciferase reporter assay was employed to detect the direct binding of miR-29b to DNMT3A/3B 3′ UTRs. Co-IP was utilized for investigating Id-1 binding activity. Results: miR-29b was negatively correlated with DNMT3A/3B expression at the cellular/histological levels. miR-29b silencing was correlated with increased DNMT3A/3B levels, whereasmiR-29b over-expression caused DNMT3A/3B down-regulation. Luciferase reporter assays confirmed that the miR-29b-mediated downregulation of DNMT3A/3Boccurred through the direct targeting of theirmRNAs'3'-UTRs,whereasBGS assays found that DNMT3A/3B knockdown increased miR-29b expression via CpG island promoter hypomethylation, thus suggesting a crucial crosstalk betweenmiR-29b and DNMT3A/3B via a double-negative feedback loop. Co-IP assay confirmed direct binding between DNMT3A and Id-1. Conclusion: Taken together, our study sheds light on a novel epigenetic circuitry regulating EOC progression and may provide novel options for miR-29b-based epi-therapeutic approaches for future EOC treatment.

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