Chemotherapeutics are validated conventional treatments for patients with advanced cancer. However, with continual application of chemotherapeutics, chemoresistance, which is often predictive of poor prognosis, has gradually become a concern in recent years. Circular RNAs (circRNAs), a class of endogenous noncoding RNAs (ncRNAs) with a closed-loop structure, have been reported to be notable targets and markers for the prognosis, diagnosis, and treatment of many diseases, particularly cancer. Although dozens of studies have shown that circRNAs play major roles in drug-resistance activity in tumors, the mechanisms by which circRNAs affect chemoresistance have yet to be explored. In this review, we describe the detailed mechanisms of circRNAs and chemotherapeutics in various cancers and summarize potential therapeutic targets for drug-resistant tumors.
Background: Long noncoding RNAs (lncRNAs) are considered critical regulators in cancers; however, the clinical significance and mechanisms of MAPKAPK5-AS1 (hereinafter referred to as MK5-AS1) in colorectal cancer (CRC) remain mostly unknown. Methods: In this study, quantitative real-time PCR (qPCR) and western blotting were utilized to detect the levels of MK5-AS1, let-7f-1-3p and MK5 (MAPK activated protein kinase 5) in CRC tissues and cell lines. The biological functions of MK5-AS1, let-7f-1-3p and MK5 in CRC cells were explored using Cell Counting Kit-8 (CCK8), colony formation and transwell assays. The potential mechanisms of MK5-AS1 were evaluated by RNA pull-down, RNA immunoprecipitation (RIP), dual luciferase reporter assay, chromatin immunoprecipitation (ChIP) and bioinformatics analysis. The effects of MK5-AS1 and MK5 on CRC were investigated by a xenotransplantation model. Results: We confirmed that MK5-AS1 was significantly increased in CRC tissues. Knockdown of MK5-AS1 suppressed cell migration and invasion in vitro and inhibited lung metastasis in mice. Mechanistically, MK5-AS1 regulated SNAI1 expression by sponging let-7f-1-3p and cis-regulated the adjacent gene MK5. Moreover, MK5-AS1 recruited RBM4 and eIF4A1 to promote the translation of MK5. Our study verified that MK5 promoted the phosphorylation of c-Jun, which activated the transcription of SNAI1 by directly binding to its promoter. Conclusions: MK5-AS1 cis-regulated the nearby gene MK5 and acted as a let-7f-1-3p sponge, playing a vital role in CRC tumorigenesis. This study could provide novel insights into molecular therapeutic targets of CRC.
Background Tumorigenesis is a complex and multistep process characterized by the progressive acquisition of various hallmarks, including unlimited proliferation, resistance to apoptosis, and increased invasiveness and metastasis. However, the molecular mechanisms underlying tumorigenesis remain poorly understood. Methods An in vivo genome-wide CRISPR–Cas9 screen was employed to identify tumor suppressor genes (TSG). The expression correlation analysis for candidate TSGs was performed in normal and cancer cells using TCGA database. To evaluate the role of FER in tumorigenesis, we firstly used publicly single-cell RNA sequencing data to investigate the association of FER expression and normal cell malignant transformation. Next, we established FER-knockout and -knockdown models in BEAS-2B and MCF10A cell lines. Colony formation assay, cell proliferation assay, EdU assay and apoptosis assay were conducted to determine the role of FER in tumorigenesis. Then RNA-seq was performed to explore the mechanism underlying the role of FER in inhibiting tumorigenesis. Additionally, Pan-Cancer analysis was used to analysis the role of FER in tumor progression. Results In our CRISPR–Cas9 screen, we identified 20 candidate genes, among which FER exhibited the strongest negative correlation with tumorigenesis. Normal cells with low FER expression exhibited elevated malignant transformation potential and stemness properties. FER knockout promoted the tumorigenesis of differentiated epithelial cells by reprogramming them into a cancer stem cell (CSC)-like state, characterized by high colony-forming efficiency and suspension growth ability, increased metabolic activity, dedifferentiation properties, and immune evasion. Furthermore, tumors with low FER expression exhibited poor prognosis and a noticeable CSC-like state. Conclusion Taken together, our findings not only provide insights into the essential role of FER as a stemness barrier in malignant cells during tumor initiation and progression but also highlight its potential as a target for future clinical diagnosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.