Non-Coding RNAs Associated With Radioresistance in Triple-Negative Breast Cancer

Aranza-Martínez, Alberto; Sánchez-Pérez, Julio; Brito-Elias, Luis; López‐Camarillo, César; León, David Cantú de; Pérez‐Plasencia, Carlos; López–Urrutia, Eduardo

doi:10.3389/fonc.2021.752270

Cited by 16 publications

(3 citation statements)

References 139 publications

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“…Radiotherapy is an important option for BRCA, especially for the highly malignant and advanced cancers [ 5 – 7 ]. This sort of therapy uses ionizing radiation (such as X-rays and γ-rays) and has substantially improved the prognosis and survival of BRCA patients after mastectomy [ 8 ]. However, the adaptive radioresistance that promotes metastatic and recurrent disease remains a major problem [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

LINC00963-FOSB-mediated transcription activation of UBE3C enhances radioresistance of breast cancer cells by inducing ubiquitination-dependent protein degradation of TP73

Wang,

Liu,

Liu

et al. 2023

J Transl Med

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Background The ubiquitin protein ligase E3C (UBE3C) has been reported to play an oncogenic role in breast cancer (BRCA). This work further investigates the effect of UBE3C on the radioresistance of BRCA cells. Methods Molecules linking to radioresistance in BRCA were identified by analyzing two GEO datasets, GSE31863 and GSE101920. UBE3C overexpression or knockdown was induced in parental or radioresistant BRCA cells, followed by irradiation treatment. The malignant properties of cells in vitro, and the growth and metastatic activity of cells in nude mice, were analyzed. Downstream target proteins, as well as upstream transcriptional regulators of UBE3C, were predicted by bioinformatics tools. Molecular interactions were confirmed by immunoprecipitation and immunofluorescence assays. Furthermore, artificial alterations of TP73 and FOSB were induced in the BRCA cells for functional rescue assays. Results According to bioinformatics analyses, UBE3C expression was linked to radioresistance in BRCA. UBE3C knockdown in radioresistant BRCA cells reduced while its overexpression in parental BRCA cells increased the radioresistance of cells in vitro and in vivo. UBE3C, which induced ubiquitination-dependent protein degradation of TP73, was transcriptionally activated by FOSB. The radioresistance of cancer cells was blocked by TP73 overexpression or FOSB knockdown. Additionally, LINC00963 was found to be responsible for the recruitment of FOSB to the UBE3C promoter for transcription activation. Conclusion This work demonstrates that LINC00963 induces nuclear translocation of FOSB and the consequent transcription activation of UBE3C, which enhances radioresistance of BRCA cells by inducing ubiquitination-dependent protein degradation of TP73. Graphical Abstract

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Section: Introductionmentioning

confidence: 99%

LINC00963-FOSB-mediated transcription activation of UBE3C enhances radioresistance of breast cancer cells by inducing ubiquitination-dependent protein degradation of TP73

Wang,

Liu,

Liu

et al. 2023

J Transl Med

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“…It was proposed that in unperturbed cells, Wee1 protects replication forks and prevents generation of DNA damage by inhibiting the Mus81 endonuclease ( 29 ). Several studies have indicated that Wee1 levels are regulated by non-coding RNAs, which could impact cellular sensitivity to genotoxic agents ( 30 ).…”

Section: The Kinase Wee1 a Gatekeeper At Several Cell Cycle Checkpointsmentioning

confidence: 99%

Targeting the DNA Damage Response for Cancer Therapy by Inhibiting the Kinase Wee1

Chan

Gamper

2022

Front. Oncol.

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Cancer cells typically heavily rely on the G2/M checkpoint to survive endogenous and exogenous DNA damage, such as genotoxic stress due to genome instability or radiation and chemotherapy. The key regulator of the G2/M checkpoint, the cyclin-dependent kinase 1 (CDK1), is tightly controlled, including by its phosphorylation state. This posttranslational modification, which is determined by the opposing activities of the phosphatase cdc25 and the kinase Wee1, allows for a more rapid response to cellular stress than via the synthesis or degradation of modulatory interacting proteins, such as p21 or cyclin B. Reducing Wee1 activity results in ectopic activation of CDK1 activity and drives premature entry into mitosis with unrepaired or under-replicated DNA and causing mitotic catastrophe. Here, we review efforts to use small molecule inhibitors of Wee1 for therapeutic purposes, including strategies to combine Wee1 inhibition with genotoxic agents, such as radiation therapy or drugs inducing replication stress, or inhibitors of pathways that show synthetic lethality with Wee1. Furthermore, it become increasingly clear that Wee1 inhibition can also modulate therapeutic immune responses. We will discuss the mechanisms underlying combination treatments identifying both cell intrinsic and systemic anti-tumor activities.

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“…However, many studies on tumor radioresistance have reported changes in the expression of microRNAs (miRNAs), which are small, well-known ncRNAs that modulate the expression of many genes belonging to different pathways [ 86 ]. Thanks to genome-wide analyses carried out by microarray and RNA sequencing technologies, it is possible to identify differentially expressed miRNA species in radioresistant lung [ 87 ], breast [ 88 , 89 ], nasopharyngeal [ 90 ], prostate [ 91 ], rectal [ 65 ], head and neck, and cervical tumors [ 89 ].…”

Section: Molecular and Cellular Features Associated With Radioresistancementioning

confidence: 99%

Biological Mechanisms to Reduce Radioresistance and Increase the Efficacy of Radiotherapy: State of the Art

Busato

Khouzai

Mognato

2022

IJMS

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Cancer treatment with ionizing radiation (IR) is a well-established and effective clinical method to fight different types of tumors and is a palliative treatment to cure metastatic stages. Approximately half of all cancer patients undergo radiotherapy (RT) according to clinical protocols that employ two types of ionizing radiation: sparsely IR (i.e., X-rays) and densely IR (i.e., protons). Most cancer cells irradiated with therapeutic doses exhibit radio-induced cytotoxicity in terms of cell proliferation arrest and cell death by apoptosis. Nevertheless, despite the more tailored advances in RT protocols in the last few years, several tumors show a relatively high percentage of RT failure and tumor relapse due to their radioresistance. To counteract this extremely complex phenomenon and improve clinical protocols, several factors associated with radioresistance, of both a molecular and cellular nature, must be considered. Tumor genetics/epigenetics, tumor microenvironment, tumor metabolism, and the presence of non-malignant cells (i.e., fibroblast-associated cancer cells, macrophage-associated cancer cells, tumor-infiltrating lymphocytes, endothelial cells, cancer stem cells) are the main factors important in determining the tumor response to IR. Here, we attempt to provide an overview of how such factors can be taken advantage of in clinical strategies targeting radioresistant tumors.

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Non-Coding RNAs Associated With Radioresistance in Triple-Negative Breast Cancer

Cited by 16 publications

References 139 publications

LINC00963-FOSB-mediated transcription activation of UBE3C enhances radioresistance of breast cancer cells by inducing ubiquitination-dependent protein degradation of TP73

LINC00963-FOSB-mediated transcription activation of UBE3C enhances radioresistance of breast cancer cells by inducing ubiquitination-dependent protein degradation of TP73

Targeting the DNA Damage Response for Cancer Therapy by Inhibiting the Kinase Wee1

Biological Mechanisms to Reduce Radioresistance and Increase the Efficacy of Radiotherapy: State of the Art

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