Circular RNAs Modulate Cancer Hallmark and Molecular Pathways to Support Cancer Progression and Metastasis

Simple Summary Circular RNAs (circRNA) are a type of RNA molecule of circular shape that are now being extensively studied due to the important roles they play in different biological processes. In addition, they were also shown to be implicated in disease such as cancer. Cancer is a complex process which is often defined by a combination of specific processes called cancer hallmarks. In this review, we summarize the literature on circRNAs in cancer and classify them as being implicated in specific cancer hallmarks. Abstract Circular RNAs (circRNAs) are noncoding products of backsplicing of pre-mRNAs which have been established to possess potent biological functions. Dysregulated circRNA expression has been linked to diseases including different types of cancer. Cancer progression is known to result from the dysregulation of several molecular mechanisms responsible for the maintenance of cellular and tissue homeostasis. The dysregulation of these processes is defined as cancer hallmarks, and the molecular pathways implicated in them are regarded as the targets of therapeutic interference. In this review, we summarize the literature on the investigation of circRNAs implicated in cancer hallmark molecular signaling. First, we present general information on the properties of circRNAs, such as their biogenesis and degradation mechanisms, as well as their basic molecular functions. Subsequently, we summarize the roles of circRNAs in the framework of each cancer hallmark and finally discuss the potential as therapeutic targets.

• Publication year

  2022

• Venue

  Cancers

• Publication date

  2022-02-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3390/cancers14040862PMID 35205610PMCID 8869994
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• CircRNAs: role in human diseases and potential use as biomarkers

  2021cited by this paper
• Silencing of circRNA circ_0001666 Represses EMT in Pancreatic Cancer Through Upregulating miR-1251 and Downregulating SOX4

  2021cited by this paper
• Cancer-related circular RNA: diverse biological functions

  2021cited by this paper
• CircZKSCAN1 Suppresses Hepatocellular Carcinoma Tumorigenesis by Regulating miR-873-5p/Downregulation of Deleted in Liver Cancer 1

  2021cited by this paper
• Optimized RNA-targeting CRISPR/Cas13d technology outperforms shRNA in identifying functional circRNAs

  2021cited by this paper
• Targeting circular RNAs as a therapeutic approach: current strategies and challenges

  2021cited by this paper
• Five Circular RNAs in Metabolism Pathways Related to Prostate Cancer

  2021cited by this paper
• circST6GALNAC6 suppresses bladder cancer metastasis by sponging miR-200a-3p to modulate the STMN1/EMT axis

  2021cited by this paper
• Engineering highly efficient backsplicing and translation of synthetic circRNAs

  2021cited by this paper
• CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129

  2021cited by this paper
• The Emerging Role of the Interactions between Circular RNAs and RNA-binding Proteins in Common Human Cancers

  2021cited by this paper
• A Circular RNA, Cholangiocarcinoma‐Associated Circular RNA 1, Contributes to Cholangiocarcinoma Progression, Induces Angiogenesis, and Disrupts Vascular Endothelial Barriers

  2021cited by this paper
• Structured elements drive extensive circular RNA translation.

  2021cited by this paper
• CircASH2L Promotes Ovarian Cancer Tumorigenesis, Angiogenesis, and Lymphangiogenesis by Regulating the miR-665/VEGFA Axis as a Competing Endogenous RNA

  2020cited by this paper
• Mapping a Circular RNA–microRNA–mRNA-Signaling Regulatory Axis that Modulates Stemness Properties of Cancer Stem Cell Populations in Colorectal Cancer Spheroid Cells

  2020cited by this paper
• CircRNA inhibits DNA damage repair by interacting with host gene

  2020cited by this paper
• CircIL4R facilitates the tumorigenesis and inhibits ferroptosis in hepatocellular carcinoma by regulating the miR‐541‐3p/GPX4 axis

  2020cited by this paper
• An in vivo strategy for knockdown of circular RNAs

  2020cited by this paper
• Circular RNA cIARS regulates ferroptosis in HCC cells through interacting with RNA binding protein ALKBH5

  2020cited by this paper
• A novel circular RNA, circ-CCAC1, contributes to CCA progression, induces angiogenesis, and disrupts vascular endothelial barriers.

  2020cited by this paper
• Circular RNA circ-CPA4/ let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC)

  2020cited by this paper
• circRNA-UBAP2 promotes the proliferation and inhibits apoptosis of ovarian cancer though miR-382-5p/PRPF8 axis

  2020cited by this paper
• CircAGFG1 drives metastasis and stemness in colorectal cancer by modulating YY1/CTNNB1

  2020cited by this paper
• Competing Endogenous RNAs, Non-Coding RNAs and Diseases: An Intertwined Story

  2020cited by this paper
• CircRNA circ_POLA2 promotes lung cancer cell stemness via regulating the miR‐326/GNB1 axis

  2020cited by this paper
• Circular RNA and tumor microenvironment

  2020cited by this paper
• The circular RNA 001971/miR-29c-3p axis modulates colorectal cancer growth, metastasis, and angiogenesis through VEGFA

  2020cited by this paper
• Wnts and the hallmarks of cancer

  2020cited by this paper
• Circular RNA circBFAR promotes the progression of pancreatic ductal adenocarcinoma via the miR-34b-5p/MET/Akt axis

  2020cited by this paper
• Structure-Mediated Degradation of CircRNAs.

  2020cited by this paper
• The circular RNA CDR1as regulate cell proliferation via TMED2 and TMED10

  2020cited by this paper
• Screening for functional circular RNAs using the CRISPR–Cas13 system

  2020cited by this paper
• Targeting apoptosis in cancer therapy

  2020cited by this paper
• Targeting cancer stem cell pathways for cancer therapy

  2020cited by this paper
• Structure-Mediated RNA Decay by UPF1 and G3BP1.

  2020cited by this paper
• Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340

  2020cited by this paper
• Circular RNA MAPK4 (circ-MAPK4) inhibits cell apoptosis via MAPK signaling pathway by sponging miR-125a-3p in gliomas

  2020cited by this paper
• Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis

  2020cited by this paper
• EMTome: a resource for pan-cancer analysis of epithelial-mesenchymal transition genes and signatures

  2020cited by this paper
• The Emerging Picture of the Roles of CircRNA-CDR1as in Cancer

  2020cited by this paper
• CircRNA EPHB4 modulates stem properties and proliferation of gliomas via sponging miR‐637 and up‐regulating SOX10

  2020cited by this paper
• The Roles of ceRNAs-Mediated Autophagy in Cancer Chemoresistance and Metastasis

  2020cited by this paper
• CircRNA CDR1as/miR-1287/Raf1 Axis Modulates Hepatocellular Carcinoma Progression Through MEK/ERK Pathway

  2020cited by this paper
• RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges

  2020cited by this paper
• Circular RNA CDR1as disrupts the p53/MDM2 complex to inhibit Gliomagenesis

  2020cited by this paper
• Withdrawn: circLgr4 drives colorectal tumorigenesis and invasion through Lgr4‐targeting peptide

  2019cited by this paper
• Inflammation and Cancer: Triggers, Mechanisms, and Consequences.

  2019cited by this paper
• circPTN sponges miR-145-5p/miR-330-5p to promote proliferation and stemness in glioma

  2019cited by this paper
• N6-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to promote colorectal liver metastasis

  2019cited by this paper
• CircRNA Cdr1as functions as a competitive endogenous RNA to promote hepatocellular carcinoma progression

  2019cited by this paper
• Tumor‐suppressive circular RNAs: Mechanisms underlying their suppression of tumor occurrence and use as therapeutic targets

  2019cited by this paper
• Differences in Tumor Microenvironment Dictate T Helper Lineage Polarization and Response to Immune Checkpoint Therapy.

  2019cited by this paper
• Circular RNA MAT2B Promotes Glycolysis and Malignancy of Hepatocellular Carcinoma Through the miR‐338‐3p/PKM2 Axis Under Hypoxic Stress

  2019cited by this paper
• Circular RNAs in Cancer: emerging functions in hallmarks, stemness, resistance and roles as potential biomarkers

  2019cited by this paper
• Circular RNA CEP128 promotes bladder cancer progression by regulating Mir‐145‐5p/Myd88 via MAPK signaling pathway

  2019cited by this paper
• Circular RNA AKT3 upregulates PIK3R1 to enhance cisplatin resistance in gastric cancer via miR-198 suppression

  2019cited by this paper
• Circular RNAs negatively regulate cancer stem cells by physically binding FMRP against CCAR1 complex in hepatocellular carcinoma

  2019cited by this paper
• Hsa_circ_0005519 increases IL‐13/IL‐6 by regulating hsa‐let‐7a‐5p in CD4+ T cells to affect asthma

  2019cited by this paper
• Circular RNA ciRS-7 promotes the proliferation and metastasis of pancreatic cancer by regulating miR-7-mediated EGFR/STAT3 signaling pathway.

  2019cited by this paper
• Inhibition of circular RNA CDR1as increases chemosensitivity of 5‐FU‐resistant BC cells through up‐regulating miR‐7

  2019cited by this paper
• The Landscape of Circular RNA in Cancer.

  2019cited by this paper
• Compound Genomic Alterations of TP53, PTEN, and RB1 Tumor Suppressors in Localized and Metastatic Prostate Cancer.

  2019cited by this paper
• Circular RNA circ0005276 promotes the proliferation and migration of prostate cancer cells by interacting with FUS to transcriptionally activate XIAP

  2019cited by this paper
• Circ-ITCH regulates triple-negative breast cancer progression through the Wnt/β-catenin pathway.

  2019cited by this paper
• Circular RNA ITCH: A novel tumor suppressor in multiple cancers.

  2019cited by this paper
• Circular RNA circFGFR1 promotes progression and anti-PD-1 resistance by sponging miR-381-3p in non-small cell lung cancer cells

  2019cited by this paper
• CircACC1 Regulates Assembly and Activation of AMPK Complex under Metabolic Stress.

  2019cited by this paper
• Circular RNA: The main regulator of energy metabolic reprogramming in cancer cells

  2019cited by this paper
• Non-coding RNA and Lung Cancer Progression.

  2019cited by this paper
• Structure and Degradation of Circular RNAs Regulate PKR Activation in Innate Immunity.

  2019cited by this paper
• Circular RNA circITGA7 inhibits colorectal cancer growth and metastasis by modulating the Ras pathway and upregulating transcription of its host gene ITGA7

  2018cited by this paper
• CiRS‐7 targeting miR‐7 modulates the progression of non‐small cell lung cancer in a manner dependent on NF‐κB signalling

  2018cited by this paper
• RETRACTED ARTICLE: CircHIPK3 promotes colorectal cancer growth and metastasis by sponging miR-7

  2018cited by this paper
• Emerging landscape of circular RNAs in lung cancer.

  2018cited by this paper
• Tumor-released exosomal circular RNA PDE8A promotes invasive growth via the miR-338/MACC1/MET pathway in pancreatic cancer.

  2018cited by this paper
• Circular RNA circ-ITCH inhibits bladder cancer progression by sponging miR-17/miR-224 and regulating p21, PTEN expression

  2018cited by this paper
• Overexpression of Circular RNA ciRS‐7 Abrogates the Tumor Suppressive Effect of miR‐7 on Gastric Cancer via PTEN/PI3K/AKT Signaling Pathway

  2018cited by this paper
• Anticancer chemotherapy and radiotherapy trigger both non-cell-autonomous and cell-autonomous death

  2018cited by this paper
• A circular RNA circ-DNMT1 enhances breast cancer progression by activating autophagy

  2018cited by this paper
• Overexpressed CDR1as functions as an oncogene to promote the tumor progression via miR-7 in non-small-cell lung cancer

  2018cited by this paper
• Circular RNAs: Promising Biomarkers for Human Diseases

  2018cited by this paper
• Global microarray profiling identified hsa_circ_0064428 as a potential immune-associated prognosis biomarker for hepatocellular carcinoma

  2018cited by this paper
• Circular RNA F-circEA-2a derived from EML4-ALK fusion gene promotes cell migration and invasion in non-small cell lung cancer

  2018cited by this paper
• The down-regulation of hsa_circ_0012919, the sponge for miR-125a-3p, contributes to DNA methylation of CD11a and CD70 in CD4+ T cells of systemic lupus erythematous.

  2018cited by this paper
• Circular RNA hsa_circ_0008305 (circPTK2) inhibits TGF-β-induced epithelial-mesenchymal transition and metastasis by controlling TIF1γ in non-small cell lung cancer

  2018influential reference
• Circular RNA BCRC-3 suppresses bladder cancer proliferation through miR-182-5p/p27 axis

  2018cited by this paper
• Circular RNAs as Therapeutic Agents and Targets

  2018cited by this paper
• Circular RNA YAP1 inhibits the proliferation and invasion of gastric cancer cells by regulating the miR-367-5p/p27 Kip1 axis

  2018cited by this paper
• FLI1 Exonic Circular RNAs as a Novel Oncogenic Driver to Promote Tumor Metastasis in Small Cell Lung Cancer

  2018cited by this paper
• circGprc5a Promoted Bladder Oncogenesis and Metastasis through Gprc5a-Targeting Peptide

  2018cited by this paper
• Loss of Tumor Suppressor Gene Function in Human Cancer: An Overview

  2018cited by this paper
• Extensive translation of circular RNAs driven by N6-methyladenosine

  2017cited by this paper
• RNA targeting with CRISPR–Cas13

  2017cited by this paper
• The circular RNA circBIRC6 participates in the molecular circuitry controlling human pluripotency

  2017cited by this paper
• The Circular RNA Interacts with STAT3, Increasing Its Nuclear Translocation and Wound Repair by Modulating Dnmt3a and miR-17 Function.

  2017cited by this paper
• The role of exosomes and miRNAs in drug‐resistance of cancer cells

  2017cited by this paper
• CircRNAs in the brain

  2017cited by this paper
• Circular RNA profile indicates circular RNA VRK1 is negatively related with breast cancer stem cells

  2017cited by this paper
• Non-coding RNA networks in cancer

  2017cited by this paper
• Circular RNA expression profiles and features in human tissues: a study using RNA-seq data

  2017cited by this paper

• Non-coding RNAs as emerging biomarkers in melanoma.

  2026cites this paper
• Non-Coding RNAs and Liquid Biopsies: Emerging Biomarkers for Cervical Cancer.

  2025cites this paper
• Non-coding RNAs: emerging biomarkers and therapeutic targets in cancer and inflammatory diseases

  2025cites this paper
• Circular RNAs orchestrating breast cancer hallmarks: bridging tumor biology and therapy resistance

  2025cites this paper
• CircSPINT2 confers sensitivity to osimertinib via hsa-miR-1296-3p/RBP1 axis and inhibits NSCLC progression

  2025cites this paper
• The function of circular RNAs in regulating Wnt/β-catenin signaling: An innovative therapeutic strategy for breast and gynecological cancers.

  2025cites this paper
• Ferroptosis and non-coding RNAs in lung cancer: exploring molecular mechanisms and diagnostic/therapeutic implications

  2025cites this paper
• The role of circRNAs and miRNAs in drug resistance and targeted therapy responses in breast cancer

  2024cites this paper
• Circ_0027885 sponges miR-203-3p to regulate RUNX2 expression and alleviates osteoporosis progression

  2024cites this paper
• Regulatory RNAs in immunosenescence

  2024cites this paper
• METTL3-mediated m6A Modification of hsa_circ_0131922 Attenuates the Progression of Papillary Thyroid Cancer by Regulating the p53 Pathway.

  2024cites this paper
• Non-Coding RNA as a Biomarker in Lung Cancer

  2024cites this paper
• CircWDR37 promotes hepatocellular carcinoma tumorigenesis by mediating the miR-646/TRAF4 regulatory pathway.

  2024cites this paper
• Unraveling the mechanisms of glioblastoma’s resistance: investigating the influence of tumor suppressor p53 and non-coding RNAs

  2024cites this paper
• Non-Coding RNAs Modulating Estrogen Signaling and Response to Endocrine Therapy in Breast Cancer

  2023cites this paper
• Deregulated miRNAs in enzalutamide resistant prostate cancer: A comprehensive review of key molecular alterations and clinical outcomes.

  2023cites this paper
• The Talented LncRNAs: Meshing into Transcriptional Regulatory Networks in Cancer

  2023cites this paper
• circGFRA1: A circular RNA with important roles in human carcinogenesis.

  2023cites this paper
• Comprehensive circular RNA expression profile of lung adenocarcinoma with bone metastasis: Identification of potential biomarkers

  2022cites this paper
• MicroRNAs in the Regulation of Solute Carrier Proteins Behind Xenobiotic and Nutrient Transport in Cells

  2022cites this paper
• Role of circular RNAs in disease progression and diagnosis of cancers: An overview of recent advanced insights.

  2022cites this paper
• Critical Roles of Circular RNA in Tumor Metastasis via Acting as a Sponge of miRNA/isomiR

  2022cites this paper