<i>AEG-1</i> Knockdown Sensitizes Glioma Cells to Radiation Through Impairing Homologous Recombination Via Targeting <i>RFC5</i>

Zhao, Xu; Sun, Yehuan; Sun, Xin; Li, Jing; Shi, Xun; Liang, Zhinan; Ma, Yuan; Zhang, Xiaozhi

doi:10.1089/dna.2020.6287

Cited by 7 publications

(6 citation statements)

References 39 publications

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“…Overall, RFC5 (36 kDa) is a tumor suppressor and indicates poor survival in many cancers such as lung cancer and glioblastoma 42 – 44 . In our results, RFC5 expression was significant in normal vs. tumor tissue of CRC patients, and showed high intensity with IHA protein analysis, and consistent results with overall survival data of CRC patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of expression profiles and prognostic value of RFCs in colorectal cancer

Misbah,

Kumar,

Najmi

et al. 2024

Sci Rep

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Colorectal cancer (CRC) ranks among the most prevalent cancers globally, with its incidence closely tied to DNA damage. The Replication Factor C (RFC) complexes comprises five protein subunits: RFC1, RFC2, RFC3, RFC4, and RFC5. These RFC complexes play crucial roles in DNA replication, repair pathways, activities post DNA damage, and ATP-dependent processes during DNA synthesis. However, the impact of RFC complexes proteins on CRC prognosis remains unclear. To explore this, we employed a computational analysis approach, utilizing platforms such as the DepMap portal, GEPIA, DAVID Bioinformatics for KEGG pathway analysis, Human Protein Atlas (HPA), STRING, and TIMER. Our results indicate that the mRNA levels of RFC1 and RFC5 were the least expressed among CRC cell lines compared to other RFC complex subunits. Notably, low RFC1 and RFC5 expression was correlated with poor prognosis in terms of CRC patients' overall survival (OS). Immunohistochemical results from the Human Protein Atlas demonstrated medium staining for RFC1, RFC2, and RFC5 in CRC tissues. Furthermore, the low expression of RFC1 and RFC5 showed a significant correlation with high expression levels of miR-26a-5p and miR-636, impacting cell proliferation through mismatch repair, DNA replication, and the nucleotide excision repair pathway. Although the precise functions of RFC1 in cancer are still unknown, our findings suggest that the small-molecule single target, CHEMBL430483, and multiple target molecules could be potential treatments for CRC. In conclusion, the elevated expression of miR-26a-5p and miR-636 targeting RFC1 and RFC5 expression holds promise as a potential biomarker for early-stage CRC detection. These insights provide novel directions and strategies for CRC therapies.

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Section: Discussionmentioning

confidence: 99%

Identification of expression profiles and prognostic value of RFCs in colorectal cancer

Misbah,

Kumar,

Najmi

et al. 2024

Sci Rep

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“…Moreover, consistent with the upregulated IL6/JAK2/STAT3 signaling in the HRisk group, IL6 induced the polarization of M1 macrophages which led to radioresistance in HNSCC [ 36 ]. The decreased MTDH level also sensitized several cancer cells to radiotherapy, probably by the mechanism of DNA damage repair [ 27 , 37 ]. These findings highlighted the importance of these genes in radioresistance and provided further support for the efficacy of our four-gene signature.…”

Section: Discussionmentioning

confidence: 99%

“…MTDH, also known as AEG-1, is recognized as an oncogene for its association with cancer progression, invasion and radioresistance enhancement [ 37 , 47–49 ]. However, the role of MTDH in radioresistance of HNSCC remains unclear.…”

Section: Discussionmentioning

confidence: 99%

MTDH enhances radiosensitivity of head and neck squamous cell carcinoma by promoting ferroptosis based on a prognostic signature

Cao,

Ge,

Yan

et al. 2023

Journal of Radiation Research

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Ionizing radiation (IR) induces ferroptosis in head and neck squamous cell carcinoma (HNSCC). But, it remains unclear whether ferroptosis affects the prognosis of HNSCC patients after receiving radiotherapy. This study aims to develop a ferroptosis signature to predict the radiosensitivity and prognosis of HNSCC. Ferroptosis-related genes, clinical data and RNA expression profiles were obtained from the FerrDb database, The Cancer Genome Atlas and GEO database. Prognostic genes were identified by random survival forest, univariate Cox regression, Kaplan–Meier and ROC analyses. Principal component analysis, multivariate Cox regression, nomogram and DCA analyses were conducted to estimate its predictive ability. Functional enrichment and immune-related analyses were performed to explore potential biological mechanisms and tumor immune microenvironment. The effect of the hub gene on ferroptosis and radiosensitivity was verified using flow cytometry, quantitative real-time PCR and clonogenic survival assay. We constructed a ferroptosis-related signature, including IL6, NCF2, metadherin (MTDH) and CBS. We classified patients into high-risk (HRisk) and low-risk groups according to the risk scores. The risk score was confirmed to be an independent predictor for overall survival (OS). Combining the clinical stage with the risk score, we established a predictive nomogram for OS. Furthermore, pathways related to tumorigenesis and tumor immune suppression were mainly enriched in HRisk. MTDH was verified to have a potent effect on IR-induced ferroptosis and consequently promoted radiosensitivity. We constructed a ferroptosis-related signature to predict radiosensitivity and OS in HNSCC patients. MTDH was identified as a promising therapeutic target in radioresistant HNSCC patients.

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“…Mechanistically, AEG-1 knockdown impaired homologous recombination repair activity induced by IR through inhibiting RFC5 expression. Furthermore, the Kaplan-Meier analysis and multivariate Cox regression analysis indicated that high levels of AEG-1 and RFC5 were related to poor prognosis of glioma patients treated with RT [75].…”

Section: Preclinical Studiesmentioning

confidence: 97%

“…The effect of astrocyte elevated gene-1 (AEG-1) on the radiosensitivity of glioma cells has been investigated by Zhao et al [75]. Immunohistochemistry assay found that AEG-1 was generally overexpressed in glioma tissues and was correlated with poor clinicopathological features of glioma patients.…”

Section: Preclinical Studiesmentioning

confidence: 99%

Radiotherapy of High-Grade Gliomas: First Half of 2021 Update with Special Reference to Radiosensitization Studies

Fròsina

2021

IJMS

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Albeit the effort to develop targeted therapies for patients with high-grade gliomas (WHO grades III and IV) is evidenced by hundreds of current clinical trials, radiation remains one of the few effective therapeutic options for them. This review article analyzes the updates on the topic “radiotherapy of high-grade gliomas” during the period 1 January 2021–30 June 2021. The high number of articles retrieved in PubMed using the search terms (“gliom* and radio*”) and manually selected for relevance indicates the feverish research currently ongoing on the subject. During the last semester, significant advances were provided in both the preclinical and clinical settings concerning the diagnosis and prognosis of high-grade gliomas, their radioresistance, and the inevitable side effects of their treatment with radiation. The novel information concerning tumor radiosensitization was of special interest in terms of therapeutic perspective and was discussed in detail.

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AEG-1 Knockdown Sensitizes Glioma Cells to Radiation Through Impairing Homologous Recombination Via Targeting RFC5

Cited by 7 publications

References 39 publications

Identification of expression profiles and prognostic value of RFCs in colorectal cancer

Identification of expression profiles and prognostic value of RFCs in colorectal cancer

MTDH enhances radiosensitivity of head and neck squamous cell carcinoma by promoting ferroptosis based on a prognostic signature

Radiotherapy of High-Grade Gliomas: First Half of 2021 Update with Special Reference to Radiosensitization Studies

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