The effect of aberrant expression and genetic polymorphisms of Rad21 on cervical cancer biology

Li, Xia; Wang, Minjie; Li, Hongying; Tang, Xiangjing; Chen, Fei; Cui, Jinquan

doi:10.1002/cam4.1592

Cited by 15 publications

(14 citation statements)

References 36 publications

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“…Previous study identified RAD21 as a new binding partner of mutant P53 in ovarian cancer, the specific molecular mechanism by which RAD21 regulates the expression of MFAP2 and the relationship to mutant p53 in HCC remains to be investigated. 23 , 17 , 25 …”

Section: Discussionmentioning

confidence: 99%

MFAP2 Promotes the Proliferation of Cancer Cells and Is Associated With a Poor Prognosis in Hepatocellular Carcinoma

Zhu

Cheng

et al. 2020

Technol Cancer Res Treat

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Backgrounds: Microfibril-associated protein 2 (MFAP2) is an extracellular matrix protein that regulates the function of microfibrils by interacting with fibrillin. MFAP2 has been reported to play an important role in metabolic diseases and has been shown to be significantly overexpressed in head and neck squamous cell carcinoma and Hepatocellular carcinoma (HCC). However, the molecular function and prognostic value of MFAP2 have never been reported in HCC or other tumors. Methods: In the present study, expression characteristics of MFAP2 in HCC, its influence on the development of HCC, as well as its function and potential mechanism in HCC were verified by Quantitative reverse transcription-polymerase chain reaction, bioinformatics data mining and in vitro cell experiments. Results: MFAP2 was prominently high-expressed in HCC and associated with cancer stages. HCC patients with higher MFAP2 expression displayed lower overall survival (OS) and disease-specific survival(DSS), while there was no significant difference in recurrence-free survival (RFS). In vitro experiments showed that downregulation of MFAP2 inhibited proliferation, migration level of HCC cells. Transcription factors, DNA methyltransferases, immune factors may interact with MFAP2 mRNA to promote tumor progression in HCC. Conclusion: These findings suggest that MFAP2 may play a key role in the development of HCC. Therefore, MFAP2 may be a valuable prognostic marker and an effective anticancer target in HCC.

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Section: Discussionmentioning

confidence: 99%

MFAP2 Promotes the Proliferation of Cancer Cells and Is Associated With a Poor Prognosis in Hepatocellular Carcinoma

Zhu

Cheng

et al. 2020

Technol Cancer Res Treat

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“…Additionally, high RAD21 expression in patients with cervical cancer was associated with poor disease survival and involving the development of cervical cancer possibly by participating in the regulation of cell cycle and the nuclear output of the tumor suppressor gene. 17 Deb et al 18 conducted a retrospective study of 652 patients with colon cancer and found that RAD21 expression is related to disease progression, showing a positive correlation with chemotherapy in tumors harboring KRAS mutations and resistance. In breast cancer, Xu et al 19 showed that RAD21 expression correlated with early relapse.…”

Section: Discussionmentioning

confidence: 99%

High expression of RAD21 predicts poor survival in patients with operated non-small-cell lung cancer

Zhu

Gao

Yuan

et al. 2020

Tumori

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Purpose: To investigate the expression profile and prognostic value of RAD21 in patients with non-small cell lung cancer (NSCLC). Methods: A tissue microarray (TMA) containing 60 paired NSCLC tissues and peritumor tissues was purchased and another TMA containing 140 NSCLC tissues was constructed. Then, immunohistochemical staining was performed and scored. Finally, the expression profile and prognostic value of RAD21 were evaluated. Results: RAD21 was predominantly detected in the nucleus of tumor and peritumor cells. RAD21 was more highly expressed in tumor tissues compared to peritumor tissues. High RAD21 expression was correlated with more lymph node metastases and advanced pathological stage, but not with any other clinicopathological features. High RAD21 expression led to worsened overall survival (OS) and was an independent prognostic factor for worsened OS in NSCLC, especially in stage II–III. Conclusion: High RAD21 expression indicates poor survival in patients with NSCLC. RAD21 may become a novel prognostic biomarker and therapeutic target in patients with NSCLC.

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“…upregulates cell proliferation and downregulates p53 signaling [43] . In this study, we found that RAD21 and SMC3 served downstream of Wnt/β-catenin signaling and directly enhanced CENPK transcription.…”

Section: Discussionmentioning

confidence: 99%

CENPK Interacts with SOX6 to Promote Cervical Cancer Stemness and Chemoresistance Through Wnt and P53 Signaling

Lin

Wang

Liu

et al. 2021

Preprint

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Background Stemness and chemoresistance contribute to cervical cancer recurrence and metastasis. It is meaningful to develop alternative targets for eliminating cancer stem cells (CSCs) properties, suppressing metastasis, and alleviating chemoresistance in cervical cancer. This study clarifies the role of CENPK in cervical cancer stemness and chemoresistance and its clinical significance in cancer progression. Methods Human cervical cancer cell lines, xenografts, and clinical samples were used for expression and functional analysis. CENPK expression in cervical cancer was analyzed by bioinformatics based on a microarray and TCGA database and immunohistochemistry based on 119 paraffin-embedded cervical cancer specimens and 35 paraffin-embedded adjacent normal tissues in a tissue chip. Results CENPK served as an oncogene by promoting CSCs properties, DNA damage repair, epithelial-mesenchymal transition and DNA replication, thus inducing cisplatin/carboplatin resistance, cell metastasis and proliferation in cervical cancer. Intriguingly, targeting CENPK markedly prolonged the survival time of cervical cancer-bearing mice, and improved chemotherapy sensitivity of cervical cancer cells in vivo. CENPK also interacted with tumor suppressor gene SOX6 to activate Wnt signaling and inactivate p53 signaling. CENPK modulated expression of key regulators in CSCs properties, DNA damage repair, epithelial-mesenchymal transition and DNA replication by disrupting SOX6-β-catenin interaction, promoting β-catenin expression and nuclear translocation, and facilitating SOX6-mediated p53 ubiquitination and nuclear export, thus stimulating cervical cancer stemness, chemoresistance, metastasis and proliferation by. Interestingly, the RAD21/SMC3 complex, downstream targets of β-catenin, enhanced CENPK transcription to form a positive regulatory circuit through Wnt signaling. Facilitation of Wnt signaling by iRhom2 further activated the CENPK/SOX6-β-catenin-RAD21/SMC3 loop and conferred cervical cancer progression, suggesting a Wnt-p53 pathway crosstalk. Importantly, CENPK was upregulated in cervical cancer, correlated with cancer recurrence, and independently predicted poor patient prognosis. Conclusions This work identifies CENPK as a prognostic indicator and highlights targeting of CENPK as a novel strategy in the treatment of cervical cancer.

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The effect of aberrant expression and genetic polymorphisms of Rad21 on cervical cancer biology

Cited by 15 publications

References 36 publications

MFAP2 Promotes the Proliferation of Cancer Cells and Is Associated With a Poor Prognosis in Hepatocellular Carcinoma

MFAP2 Promotes the Proliferation of Cancer Cells and Is Associated With a Poor Prognosis in Hepatocellular Carcinoma

High expression of RAD21 predicts poor survival in patients with operated non-small-cell lung cancer

CENPK Interacts with SOX6 to Promote Cervical Cancer Stemness and Chemoresistance Through Wnt and P53 Signaling

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