Targeting non-coding RNAs to overcome cancer therapy resistance

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: April 13, 2022

Abstract It is now well known that non-coding RNAs (ncRNAs), rather than protein-coding transcripts, are the preponderant RNA transcripts. NcRNAs, particularly microRNAs (miRNAs), long (lncRNAs), and circular (circRNAs), widely appreciated as pervasive regulators of multiple cancer hallmarks such proliferation, apoptosis, invasion, metastasis, genomic instability. Despite recent discoveries in therapy, resistance to chemotherapy, radiotherapy, targeted immunotherapy continue be a major setback. Recent studies have shown ncRNAs also play role different therapies by rewiring essential signaling pathways. In this review, we present intricate mechanisms through which dysregulated control four types therapies. We will focus on current clinical implications biomarkers predict treatment response (intrinsic resistance) detect therapy after start (acquired resistance). Furthermore, potential targeting ncRNA overcome resistance, discuss challenges ncRNA-targeted therapy—especially development delivery systems.

Language: Английский

---

Circular RNAs in body fluids as cancer biomarkers: the new frontier of liquid biopsies

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Jan. 11, 2021

Abstract Cancer is a leading cause of death worldwide, particularly because its high mortality rate in patients who are diagnosed at late stages. Conventional biomarkers originating from blood widely used for cancer diagnosis, but their low sensitivity and specificity limit widespread application screening among the general population. Currently, emerging studies exploiting novel, highly-accurate human body fluids that obtainable through minimally invasive techniques, which defined as liquid biopsy. Circular RNAs (circRNAs) newly discovered class noncoding generated mainly by pre-mRNA splicing. Following rapid development high-throughput transcriptome analysis numerous circRNAs have been recognized to exist stably levels fluids, including plasma, serum, exosomes, urine. CircRNA expression patterns exhibit distinctly differences between with healthy controls, suggesting potentially represent novel monitoring progression. In this study, we summarized pan-cancer dataset characterized clinical applications biopsy diagnosis prognosis. addition, user-friendly web interface was developed visualize each circRNA ( https://mulongdu.shinyapps.io/circrnas_in_fluids/ ).

Language: Английский

---

Non-coding RNAs in GI cancers: from cancer hallmarks to clinical utility

Gut, Journal Year: 2020, Volume and Issue: 69(4), P. 748 - 763

Published: Feb. 7, 2020

One of the most unexpected discoveries in molecular oncology, last decades, was identification a new layer protein coding gene regulation by transcripts that do not codify for proteins, non-coding RNAs. These represent heterogeneous category interact with many types genetic elements, including regulatory DNAs, and other directly to proteins. The final outcome, malignant context, is any cancer hallmarks. Non-coding RNAs abundant type hormones contribute significantly cell-to cell communication, revealing complex interplay between tumour cells, microenvironment cells immune cells. Consequently, profiling their abundance bodily fluids became mainstream biomarker identification. Therapeutic targeting represents option clinicians currently under development. This review will present biology translational value three studied categories on RNAs, microRNAs, long circular We also focus some aspirational concepts can help development clinical applications related using pyknons discover human-specific which are expressed specifically increase efficiency immunotherapy.

Language: Английский

---

The potential of using blood circular RNA as liquid biopsy biomarker for human diseases

Protein & Cell, Journal Year: 2020, Volume and Issue: 12(12), P. 911 - 946

Published: Nov. 1, 2020

Abstract Circular RNA (circRNA) is a novel class of single-stranded RNAs with closed loop structure. The majority circRNAs are formed by back-splicing process in pre-mRNA splicing. Their expression dynamically regulated and shows spatiotemporal patterns among cell types, tissues developmental stages. CircRNAs have important biological functions many physiological processes, their aberrant implicated human diseases. Due to high stability, becoming promising biomarkers diseases, such as cardiovascular autoimmune diseases cancers. In this review, we focus on the translational potential using blood liquid biopsy for We highlight abundant expression, essential significant correlations various components peripheral blood, including whole cells extracellular vesicles. addition, summarize current knowledge circRNA disease diagnosis or prognosis.

Language: Английский

---

The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers

Cancers, Journal Year: 2021, Volume and Issue: 13(23), P. 5874 - 5874

Published: Nov. 23, 2021

The miR-200 family of microRNAs (miRNAs) includes miR-200a, miR-200b, miR-200c, miR-141 and miR-429, five evolutionarily conserved miRNAs that are encoded in two clusters hairpin precursors located on human chromosome 1 (miR-200b, miR-200a miR-429) 12 (miR-200c miR-141). mature -3p products the abundantly expressed epithelial cells, where they contribute to maintaining phenotype by repressing expression factors favor process epithelial-to-mesenchymal transition (EMT), a key hallmark oncogenic transformation. Extensive studies interactions these with cell signaling pathways indicate can exert both tumor suppressor- pro-metastatic functions, may serve as biomarkers cancers. This review provides summary role members EMT, regulate their expression, important targets for miR-200-mediated repression involved EMT. second part discusses potential utility circulating diagnostic/prognostic breast, colorectal, lung, ovarian, prostate bladder

Language: Английский

---

Comparison of the efficiency of ultrafiltration, precipitation, and ultracentrifugation methods for exosome isolation

Biochemistry and Biophysics Reports, Journal Year: 2024, Volume and Issue: 38, P. 101668 - 101668

Published: Feb. 21, 2024

Extracellular vesicles (EVs) are enclosed by a lipid-bilayer membrane and secreted all types of cells. They classified into three groups: apoptotic bodies, microvesicles, exosomes. Exosomes play number important roles in the intercellular communication crosstalk between tissues body. In this study, we use common methods based on different principles for exosome isolation, namely ultrafiltration, precipitation, ultracentrifugation. We field emission scanning electron microscopy (FESEM) dynamic light scattering (DLS) analyses characterization The functionality effect isolated exosomes viability hypoxic cells was investigated alamarBlue Flow-cytometry. results FESEM study show that ultrafiltration method isolates with higher variability shapes sizes when compared to precipitation ultracentrifugation methods. DLS mean size 122, 89, 60 nm respectively. AlamarBlue analysis increase damaged 11%, 15%, 22%, Flow-cytometry also these content live 9%, 20%, This shows characterized smaller narrow distribution. Furthermore, more homogenous particles increased efficiency protection comparison two other

Language: Английский

---

Circular RNA Splicing

Advances in experimental medicine and biology, Journal Year: 2018, Volume and Issue: unknown, P. 41 - 52

Published: Jan. 1, 2018

Language: Английский

---

Circular RNAs in cancer: Limitations in functional studies and diagnostic potential

Seminars in Cancer Biology, Journal Year: 2020, Volume and Issue: 75, P. 49 - 61

Published: Oct. 6, 2020

Circular RNAs (circRNAs) are a large class of noncoding RNAs, generated from process called back-splicing, that possess critical regulatory functions in many cellular events. A body literature has reported various circRNA and their underlying mechanisms, including sponging miRNA, exerting transcriptional translational regulation, interacting with proteins, translating into peptides proteins. CircRNA dysregulation been implicated cancers, lung, breast, liver, gastric, colorectal, ovarian cancer. They detectable bodily fluids relatively stable, making them potential cancer biomarker candidates. Furthermore, targeting expression levels is therapeutic approach for treating cancers. In this review, we describe the functional mechanisms circRNAs discuss limitations current mechanism studies. Following this, outline to be effective biomarkers cancers present circRNA-based approaches. Finally, challenges using as diagnostic tools propose future research directions.

Language: Английский

---

Non-Coding RNA: Role in Gestational Diabetes Pathophysiology and Complications

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(11), P. 4020 - 4020

Published: June 4, 2020

Gestational Diabetes Mellitus (GDM) is defined as glucose intolerance that develops in the second or third trimester of pregnancy. GDM can lead to short-term and long-term complications both mother offspring. Diagnosing treating this condition therefore great importance avoid poor pregnancy outcomes. There increasing interest finding new markers with potential diagnostic, prognostic therapeutic utility GDM. Non-coding RNAs (ncRNAs), including microRNAs, long non-coding circular RNAs, are critically involved metabolic processes their dysregulated expression has been reported several pathological contexts. The aberrant circulating placenta-related ncRNAs linked insulin resistance β-cell dysfunction, key pathophysiological features Furthermore, significant associations between altered ncRNA profiles GDM-related complications, such macrosomia trophoblast have observed. Remarkably, deregulation ncRNAs, which might be a detrimental intrauterine environment, changes target genes offspring, possibly contributing development cardiovascular diseases. In review, all recent findings on summarized, particularly focusing molecular aspects implications complex relationship.

Language: Английский

---

Circular RNA circ_001422 promotes the progression and metastasis of osteosarcoma via the miR-195-5p/FGF2/PI3K/Akt axis

Journal of Experimental & Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 40(1)

Published: July 16, 2021

Abstract Background Circular RNAs (circRNAs) are involved in diverse processes that drive cancer development. However, the expression landscape and mechanistic function of circRNAs osteosarcoma (OS) remain to be studied. Methods Bioinformatic analysis high-throughput RNA sequencing tools were employed identify differentially expressed between OS adjacent noncancerous tissues. The level circ_001422 clinical specimens cell lines was measured using qRT-PCR. association with clinicopathologic features 55 recruited patients analyzed. Loss- gain-of-function experiments conducted explore role cells. immunoprecipitation, fluorescence situ hybridization, bioinformatics database analysis, pulldown assays, dual-luciferase reporter mRNA sequencing, rescue decipher competitive endogenous regulatory network controlled by circ_001422. Results We characterized a novel abundant circRNA, circ_001422, promoted progression. Circ_001422 dramatically increased tissues compared samples. Higher correlated more advanced stage, larger tumor size, higher incidence distant metastases poorer overall survival patients. knockdown markedly repressed proliferation metastasis apoptosis cells vivo vitro, whereas overexpression exerted opposite effects. Mechanistically, interactions miR-195-5p elevated FGF2 while also initiating PI3K/Akt signaling. These events enhanced malignant characteristics Conclusions accelerates tumorigenesis modulating miR-195-5p/FGF2/PI3K/Akt axis, implying can therapeutically targeted treat OS.

Language: Английский

---