☆ 4.6 Review

Cancer quiescence: non-coding RNAs in the spotlight

TRENDS IN MOLECULAR MEDICINE (2023)

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Review Cell Biology

Epi-miRNAs: Modern mediators of methylation status in human cancers

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Summary: Methylation of DNA/RNA and proteins is crucial for cellular homeostasis and development, and disrupted methylation imprinting is strongly associated with human pathologies, especially cancer. Recent evidence has shown that miRNAs play a significant role in regulating cellular methylation profiles during cancer onset and progression. Epi-miRNAs are a novel subclass of miRNAs that have potential clinical utility in cancer diagnostics and personalized therapeutics.

WILEY INTERDISCIPLINARY REVIEWS-RNA (2023)

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Article Oncology

C4orf47 contributes to the dormancy of pancreatic cancer under hypoxic conditions

Shinjiro Nagao et al.

Summary: In our analysis of pancreatic cancer pathology, we found that C4orf47 is upregulated in hypoxic environments. Its role in cancer was unknown, so we investigated its significance in pancreatic cancer. We discovered that C4orf47 is a direct target of HIF-1 alpha and is upregulated in hypoxic conditions. It suppresses the cell cycle and inhibits cell proliferation, induces epithelial-mesenchymal transition, and enhances cell invasiveness. Additionally, C4orf47 may be involved in pancreatic cancer dormancy and serve as a prognostic biomarker for the disease.

JOURNAL OF CANCER (2023)

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Article Biochemistry & Molecular Biology

An extracellular matrix stiffness-induced breast cancer cell transcriptome resembles the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC)

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Summary: A study found that breast cancer cells exhibit different phenotypes on matrices with different stiffness, and this stiffness-associated phenotype is related to the invasiveness of breast cancer, suggesting that matrix stiffness may be one of the mechanisms driving the transition from ductal carcinoma in situ (DCIS) to invasive breast cancer.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2023)

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Review Oncology

Regulation of dormancy during tumor dissemination: the role of the ECM

Ananya Mukherjee et al.

Summary: The study of the metastatic cascade has revealed the complexity of the process and the multiple cellular states that disseminated cancer cells must go through. The tumor microenvironment, especially the extracellular matrix (ECM), plays a crucial role in regulating the transition from invasion, dormancy to proliferation during the metastatic cascade. Identifying dormant cells, their niches, and the transition to the proliferative state are active areas of investigation, and novel approaches have been developed to track dormant cells during dissemination. This review highlights the latest research on the invasive nature of disseminated tumor cells, their link to dormancy programs, and the role of the ECM in sustaining dormant niches at distant sites.

CANCER AND METASTASIS REVIEWS (2023)

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Review Oncology

Dormancy, stemness, and therapy resistance: interconnected players in cancer evolution

Federica Francescangeli et al.

Summary: The complexity of cancer poses a great challenge to current treatment protocols, leading to frequent treatment failures. Cancer cell dormancy is closely linked to the tumor's ability to survive cytotoxic challenges, metastasize, and resist immune-mediated attack. Recent studies have focused on understanding quiescent/therapy resistant cancer cells and identifying biomarkers/therapeutic targets, but there is still a lack of understanding and control over cancer dormancy in clinical settings.

CANCER AND METASTASIS REVIEWS (2023)

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Review Cell Biology

Emerging roles and functional mechanisms of PIWI-interacting RNAs

Xin Wang et al.

Summary: PIWI-interacting RNAs (piRNAs) are important small non-coding RNAs that play crucial roles in germ line development through silencing transposable elements and regulating protein-coding genes. Recent studies have advanced our understanding of piRNA biogenesis and function, and highlighted their significance in human infertility, cancer, and neurological diseases.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2023)

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Article Oncology

Circular RNA circFBXO7 attenuates non-small cell lung cancer tumorigenesis by sponging miR-296-3p to facilitate KLF15-mediated transcriptional activation of CDKN1A

Zi-Hao Wang et al.

Summary: In this study, it was found that circFBXO7 is downregulated in non-small cell lung cancer (NSCLC) tissues and cell lines, and high expression of circFBXO7 is associated with better prognosis. Overexpression of circFBXO7 inhibits cell proliferation and may function through the regulation of the miR-296-3p/KLF15/CDKN1A pathway. CircFBXO7 may serve as a potential biomarker and therapeutic target for NSCLC.

TRANSLATIONAL ONCOLOGY (2023)

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Article Cell Biology

Differential effects of the LncRNA RNF157-AS1 on epithelial ovarian cancer cells through suppression of DIRAS3-and ULK1-mediated autophagy

Pengfei Xu et al.

Summary: Analyses of several databases showed that the lncRNA RNF157-AS1 is overexpressed in epithelial ovarian cancer tissues. Suppression or overexpression of RNF157-AS1 significantly affects the proliferation, invasion, and migration of EOC cells. RNF157-AS1 interacts with HMGA1 and EZH2 proteins, regulating the expression of ULK1 and DIRAS3 and influencing autophagy.

CELL DEATH & DISEASE (2023)

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Article Multidisciplinary Sciences

Longitudinal single-cell profiling of chemotherapy response in acute myeloid leukemia

Matteo Maria Naldini et al.

Summary: Relapse in acute myeloid leukemia may be driven by the presence of leukemia stem cells. The authors use single-cell RNA sequencing to identify and characterize leukemia stem cells, and find that miR-126 is a potential marker of resistance. miR-126 high-expressing leukemia stem cells are enriched in chemotherapy-refractory AML and at relapse, and their transcriptional signature can robustly stratify patients for survival.

NATURE COMMUNICATIONS (2023)

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Article Cell Biology

5-Azacytidine- and retinoic-acid-induced reprogramming of DCCs into dormancy suppresses metastasis via restored TGF-β-SMAD4 signaling

Deepak K. Singh et al.

Summary: The combination of 5-azacytidine (AZA) and retinoic acid receptor (RAR) agonists can induce and maintain dormancy in cancer cells, effectively suppressing metastasis formation. This is achieved through the restoration of transforming growth factor b (TGF-b) signaling and anti-proliferative function, as well as the maintenance of solitary disseminated cancer cells (DCCs) in a non-proliferative state. The knockdown of SMAD4 gene can lead to resistance against AZA+RAR-induced dormancy.

CELL REPORTS (2023)

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Review Oncology

Role of tumor microenvironment in cancer progression and therapeutic strategy

Qingjing Wang et al.

Summary: Cancer is now recognized as a disease influenced by the tumor microenvironment (TME) rather than just a cellular and genetic disorder. Significant progress has been made in understanding the complexity of the TME and its impact on various anticancer therapies, particularly immunotherapies. Immunotherapy has shown promising therapeutic effects in treating solid tumors and hematological malignancies by leveraging the body's immune system to target and eliminate cancer cells. Recent advancements include the use of PD-1 and PD-L1 inhibitors, CAR-T cell therapy, and tumor vaccines. The TME plays a crucial role in tumor development, progression, and metastasis, making it an important focus for cancer immunotherapy research.

CANCER MEDICINE (2023)

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Article Biotechnology & Applied Microbiology

Genomic hallmarks and therapeutic implications of G0 cell cycle arrest in cancer

Anna J. Wiecek et al.

Summary: Researchers have developed a method to identify the non-proliferative G0 state in cancer and determine its prevalence and genomic constraints in solid primary tumors. It has been found that G0 arrest is more likely to occur in genomes that are stable, less mutated, maintain TP53 integrity, lack DNA damage repair deficiency markers, and exhibit increased APOBEC mutagenesis. Machine learning has revealed novel genomic dependencies of this process and the role of the centrosomal gene CEP89 in modulating proliferation and G0 arrest capacity. Furthermore, G0 arrest has been shown to underlie unfavorable responses to various therapies in single-cell data, which target cell cycle, kinase signaling, and epigenetic mechanisms.

GENOME BIOLOGY (2023)

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Article Multidisciplinary Sciences

Primary tumor associated macrophages activate programs of invasion and dormancy in disseminating tumor cells

Lucia Borriello et al.

Summary: This study utilizes high-resolution intravital imaging to track breast-derived metastatic cells in the lung and finds that macrophages in the primary tumor affect the dissemination and dormancy phenotypes of these cells.

NATURE COMMUNICATIONS (2022)

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Review Cell Biology

Regulation and different functions of the animal microRNA-induced silencing complex

Pierre-Marc Frederick et al.

Summary: miRNAs play a key role in gene expression regulation by forming the miRNA induced silencing complex (miRISC) with Argonaute protein to target specific mRNAs. The regulation of miRISC functions in animals involves post-translational modifications, 3' UTR environment, and interactions with other proteins. Subcellular localization and vesicular trafficking also play important roles in modulating miRISC function.

WILEY INTERDISCIPLINARY REVIEWS-RNA (2022)

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The role of RNA processing and regulation in metastatic dormancy

Kimberly A. Parker et al.

Summary: Tumor dormancy is a significant factor in metastatic diseases, and recent studies have shown that RNA processing plays a crucial role in maintaining the dormancy state. Dysregulated RNA processing is associated with tumor metastatic dormancy and recurrence.

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Circular RNAs: Characterization, cellular roles, and applications

Chu-Xiao Liu et al.

Summary: In this review, we discuss the methods used in circular RNA studies and the current understanding of their regulatory roles and potential applications. Circular RNAs can modulate transcription and splicing, regulate the stability and translation of mRNAs, interfere with signaling pathways, and play important roles in cellular processes and immune responses.

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DTX-P7, a peptide-drug conjugate, is highly effective for non-small cell lung cancer

Yao Jiang et al.

Summary: Despite the successful use of molecular targeted therapy and immunotherapy, only a small subset of patients can benefit from these treatments. Chemotherapy remains the main treatment for most tumors, but its non-selective effects on healthy tissues and developing resistance are major obstacles. In this study, a new conjugate called DTX-P7 was developed, which specifically targeted and inhibited tumor growth in non-small cell lung cancer. DTX-P7 induced unfolded protein response and subsequent apoptosis, effectively killing the dormant cancer stem cells. Therefore, DTX-P7 shows promise as a potential anticancer therapeutic.

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Article Multidisciplinary Sciences

MicroRNA networks in FLT3-ITD acute myeloid leukemia

Dinh Hoa Hoang et al.

Summary: In acute myeloid leukemia (AML), FLT3-ITD regulates the biogenesis of miR-126 and miR-155. FLT3-ITD induces the expression of miR-155, which down-regulates SHIP1 and increases AKT activity, leading to increased cell cycle progression. Additionally, miR-155 down-regulates SPRED1 and blocks the biogenesis of miR-126, resulting in decreased levels of mature miR-126.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

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Article Oncology

Role of Neural (N)-Cadherin in Breast Cancer Cell Stemness and Dormancy in the Bone Microenvironment

Antonio Maurizi et al.

Summary: This study identified the role of N-Cadherin in breast cancer cell dormancy and stemness. Breast cancer cells that interact with spindle-shaped N-Cadherin(+) Osteoblasts (SNOs) become dormant, and N-Cadherin mediates the adhesion of breast cancer cells to SNOs. The study also revealed differences in the role of N-Cadherin between human and mouse breast cancer cell lines.

CANCERS (2022)

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Article Oncology

Resveratrol Contrasts IL-6 Pro-Growth Effects and Promotes Autophagy-Mediated Cancer Cell Dormancy in 3D Ovarian Cancer: Role of miR-1305 and of Its Target ARH-I

Andrea Esposito et al.

Summary: Tumor dormancy is a challenging period to target pharmacologically, with inflammatory cytokines in the tumor microenvironment playing a role. IL-6 inhibits autophagy in ovarian cancer cells by downregulating ARH-I via miRNAs, while resveratrol (RV) has the opposite effect. Maintaining cell dormancy with RV may be a therapeutic option to prevent cancer cell awakening in response to a permissive microenvironment.

CANCERS (2022)

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Article Medicine, Research & Experimental

All-trans retinoic acid-mediated miR-30a up-regulation suppresses autophagy and sensitizes gastric cancer cells to cisplatin

Asadollah Abbasi et al.

Summary: The study suggests that miR-30a/autophagy signaling plays a critical role in regulating the chemoresistance of GC cells, which could be modulated by ATRA.

LIFE SCIENCES (2022)

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Article Biochemistry & Molecular Biology

MARCKSL1-2 reverses docetaxel-resistance of lung adenocarcinoma cells by recruiting SUZ12 to suppress HDAC1 and elevate miR-200b

Min Jiang et al.

Summary: In this study, researchers found that MARCKSL1-2 alleviated DTX resistance in LAD cells by abolishing the inhibitory effect of HDAC1 on miR-200b via the recruitment of SUZ12. MARCKSL1-2 could be a promising target to improve the chemotherapy of LAD.

MOLECULAR CANCER (2022)

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Article Biochemistry & Molecular Biology

Osteoblastic protein kinase D1 contributes to the prostate cancer cells dormancy via GAS6-circadian clock signaling

Guihuan Li et al.

Summary: Disseminated prostate cancer cells can go into a dormant state in the bone marrow with the help of osteoblastic PKD1/CREB1/GAS6 signaling. Dormant tumor cells are maintained in a non-proliferative state and can later develop into metastatic lesions. The circadian clock plays a crucial role in regulating the dormancy of prostate cancer cells. These findings provide insights into the mechanisms of tumor dormancy and highlight the potential importance of targeting circadian clock molecules for cancer treatment.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH (2022)

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Article Multidisciplinary Sciences

Epithelial-mesenchymal plasticity determines estrogen receptor positive breast cancer dormancy and epithelial reconversion drives recurrence

Patrick Aouad et al.

Summary: This study provides a new method to study the dormant state of estrogen receptor alpha-positive breast cancer (ER+ BC) and reveals the underlying mechanisms. The researchers found that disseminated ER+ BC cells proliferate slower and exhibit characteristics of epithelial-mesenchymal plasticity, which are crucial for maintaining the dormant state. They also discovered that forced expression of E-cadherin allows ER+ BC cells to overcome dormancy.

NATURE COMMUNICATIONS (2022)

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Article Oncology

Mesenchymal Stem Cell-Secreted Extracellular Vesicles Instruct Stepwise Dedifferentiation of Breast Cancer Cells into Dormancy at the Bone Marrow Perivascular Region

Oleta A. Sandiford et al.

Summary: The early dormancy and dedifferentiation process of breast cancer cells in the bone marrow perivascular niche involves mesenchymal stem cell-derived exosomes, indicating a potential target for therapeutic intervention.

CANCER RESEARCH (2021)

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Review Cell Biology

Gene regulation by long non-coding RNAs and its biological functions

Luisa Statello et al.

Summary: Recent studies have shed new light on the biogenesis and functions of long non-coding RNAs (lncRNAs), showcasing their diverse roles in gene regulation and signaling pathways, particularly in the contexts of neuronal disorders, immune responses, and cancer. The discovery of unique biogenesis pathways and subcellular localizations of lncRNAs has opened up potential therapeutic avenues for targeting lncRNAs in various biological and pathophysiological conditions.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2021)

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FUCCI-Red: a single-color cell cycle indicator for fluorescence lifetime imaging

Marina V. Shirmanova et al.

Summary: The study introduced a single-color variant called FUCCI-Red that utilizes two red fluorescent proteins with distinct fluorescence lifetimes to monitor cell cycle progression. The utility of FUCCI-Red was demonstrated through visualizing cell cycle progression in 2D and 3D cultures and monitoring tumor development in vivo.

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The ER stress response mediator ERO1 triggers cancer metastasis by favoring the angiogenic switch in hypoxic conditions

Ersilia Varone et al.

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ONCOGENE (2021)

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Targeting miR-126 in inv(16) acute myeloid leukemia inhibits leukemia development and leukemia stem cell maintenance

Lianjun Zhang et al.

Summary: The study elucidates that aberrant expression of miR-126 in inv(16) AML is directly induced by the CBFB-MYH11 fusion gene, promoting AML development and maintaining leukemia stem cells. This highlights miR-126 as a therapeutic target for inv(16) AML patients.

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Huafeng Wang et al.

Summary: The study identified the crucial role of miR-126 in maintaining MDS HSPCs and suggested that therapeutic targeting of miR-126 could be a novel approach in treating MDS. Inhibiting miR-126 expression reduced quiescence and self-renewal capacity of MDS HSPCs and alleviated MDS symptoms. The anti-miR-126 oligodeoxynucleotide miRisten showed therapeutic effects on human MDS HSPCs while sparing normal HSPCs.

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Isabel Pereira-Castro et al.

Summary: Selective polyadenylation (APA) fine-tunes gene expression and controls mRNA fate and function in different cellular states. Different lengths of 3'-UTRs are associated with specific cellular states and diseases, with short 3'-UTRs linked to proliferative and cancer cells, and long 3'-UTRs mainly found in polarized and differentiated cells.

WILEY INTERDISCIPLINARY REVIEWS-RNA (2021)

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Long non-coding RNA NR2F1-AS1 induces breast cancer lung metastatic dormancy by regulating NR2F1 and ΔNp63

Yingjie Liu et al.

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