HPV‐<i>CCDC106</i> integration promotes cervical cancer progression by facilitating the high expression of CCDC106 after HPV E6 splicing

Zhi, Wenhua; Ye, Wei; Lazare, Cordelle; Meng, Yifan; Wu, Ping; Gao, Peipei; Lin, Shitong; Peng, Ting; Chu, Tian; Liu, Binghan; Ding, Wencheng; Cao, Canhui; Wu, Peng

doi:10.1002/jmv.28009

Cited by 14 publications

(14 citation statements)

References 45 publications

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“…To date, many studies have found that CCDC106 interacts with p53, resulting in p53 degradation in cancer cells and promoting cell proliferation 1,3,4,12 . In this work, we provide evidence that the C-terminal domain of the CCDC106 protein (CCDC106-CTD) directly interacts with the N-terminal domain of the p53 protein.…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanism of CCDC106 regulating the p53-Mdm2/MdmX signal axis

Zhou

Cheng

et al. 2023

Preprint

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The tumor suppressor p53 (p53) is regulated by murine double minute 2 (Mdm2) and its homologous MdmX in maintaining the p53 basal level. The overexpressed Mdm2/MdmX inhibit the cellular p53 activity, highly relevant to cancer occurrence. The coiled-coil domain-containing protein 106 (CCDC106) has been identified as a p53-interacting partner. However, its molecular mechanism is still elusive. Here we show that CCDC106 functions as a signaling regulator of the p53-Mdm2/MdmX axis mediated by cellular p53. We identified that CCDC106 directly interacts with the p53 transactivation domain by competing with Mdm2 and MdmX. The CCDC106 overexpression downregulates the cellular level of p53 and Mdm2/MdmX, and the decreased p53 reversibly downregulates the cellular level of CCDC106. Our work not only provides a molecular mechanism of CCDC106 regulating the cellular levels of p53 and Mdm2/MdmX, but also suggests that the CCDC106-p53 interaction as a novel target for cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Molecular mechanism of CCDC106 regulating the p53-Mdm2/MdmX signal axis

Zhou

Cheng

et al. 2023

Preprint

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“…Total proteins were obtained by lysing cells using RIPA lysis supplied with protease inhibitors (HY‐K0010, MCE). Equal quality proteins were then subjected to sodium dodecyl sulphate‐polyacrylamide gel electrophoresis (8012011, BioSci) gel electrophoresis and transferred onto polyvinylidene fluoride (PVDF) membrane (10600023, GE) at 4°C, respectively 30 . The PVDF membranes were incubated with 5% bovine serum albumin (Servicebio) and primary antibodies sequentially.…”

Section: Methodsmentioning

confidence: 99%

“…Equal quality proteins were then subjected to sodium dodecyl sulphatepolyacrylamide gel electrophoresis (8012011, BioSci) gel electrophoresis and transferred onto polyvinylidene fluoride (PVDF) membrane (10600023, GE) at 4°C, respectively. 30 The PVDF membranes were incubated with 5% bovine serum albumin (Servicebio) and primary antibodies sequentially. The details of primary antibodies were as follows: BaK…”

Section: Western Blottingmentioning

confidence: 99%

“…The Protein A/G Magnetic Beads kit (HY-K0202-1, MCE) was used to perform the Co-IP assay according to the manufacturer's instructions. 30 The Protein A/G Magnetic Beads were subjected to resuspension, PIK3CA (1:50, #4249, CST) binding, immunoprecipitation of the target antigen, and elution processes. ATR (1:1000, #2790, CST) was detected by Western Blot.…”

Section: Co-immunoprecipitation (Co-ip)mentioning

confidence: 99%

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Genomic analysis of cervical carcinoma identifies Alpelisib as a therapeutic option for PIK3CA‐mutant cervical carcinoma via the PI3K/AKT pathway

Wei

Lin

Zhi

et al. 2023

Journal of Medical Virology

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Cervical carcinoma is a serious type of gynecological cancer that can affect women of all ages. Cervical carcinoma presents challenges for precision medicine, as not all tumors have specific gene mutations or alterations that can be targeted with existing drugs. Nonetheless, there are some promising targets in cervical carcinoma. Herein, genomic mutation data from The Cancer Genome Atlas and Catalogue of Somatic Mutations in Cancer were used to identify genomic targets for cervical carcinoma. PIK3CA was the most mutant gene among the promising targets, especially in cervical squamous cell carcinoma, and the mutated genes of cervical carcinoma were enriched in the RTK/PI3K/MAPK and Hippo pathways. In vitro, PIK3CA‐mutant cervical cancer cell lines showed higher sensitivity to Alpelisib than cancer cells without the PIK3CA mutation and the normal cells (HCerEpic). Protein–protein networks and co‐immunoprecipitation of PIK3CA revealed reduced interaction between p110α and ATR in PIK3CA‐mutant cervical cancer cells, which were sensitive to the combination of Alpelisib and cisplatin in vivo. Furthermore, Alpelisib significantly suppressed the proliferation and migration of PIK3CA‐mutant cervical cancer cells via inhibition of the AKT/mTOR pathway. Overall, Alpelisib showed antitumor effects and enhance cisplatin efficacy in PIK3CA‐mutant cervical cancer cells via PI3K/AKT pathways. Our study demonstrated the therapeutic potential of Alpelisib in PIK3CA‐mutant cervical carcinoma, which provides insights into precision medicine in cervical carcinoma.

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“…This depression of transcription and stabilization of fusion transcripts containing E6 and E7 synergistically intensify HPV oncogene expression 214 . Integrated tumors frequently manifest elevated levels of E6 splicing, such as E6*I 215 . Highly expressed HPV‐human fusion transcripts, such as HPV16 E6*I‐E7‐E1(SD880)‐human gene, drive cervical carcinogenesis, culminating in the overexpression of E6*I and E7 216 .…”

Section: Hpv and Its Pathogenesismentioning

confidence: 99%

Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions

Ye,

Zheng,

et al. 2023

MedComm

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Human papillomavirus (HPV) is the most prevalent sexually transmitted virus globally. Persistent high‐risk HPV infection can result in cervical precancerous lesions and cervical cancer, with 70% of cervical cancer cases associated with high‐risk types HPV16 and 18. HPV infection imposes a significant financial and psychological burden. Therefore, studying methods to eradicate HPV infection and halt the progression of precancerous lesions remains crucial. This review comprehensively explores the mechanisms underlying HPV‐related cervical lesions, including the viral life cycle, immune factors, epithelial cell malignant transformation, and host and environmental contributing factors. Additionally, we provide a comprehensive overview of treatment methods for HPV‐related cervical precancerous lesions and cervical cancer. Our focus is on immunotherapy, encompassing HPV therapeutic vaccines, immune checkpoint inhibitors, and advanced adoptive T cell therapy. Furthermore, we summarize the commonly employed drugs and other nonsurgical treatments currently utilized in clinical practice for managing HPV infection and associated cervical lesions. Gene editing technology is currently undergoing clinical research and, although not yet employed officially in clinical treatment of cervical lesions, numerous preclinical studies have substantiated its efficacy. Therefore, it holds promise as a precise treatment strategy for HPV‐related cervical lesions.

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HPV‐CCDC106 integration promotes cervical cancer progression by facilitating the high expression of CCDC106 after HPV E6 splicing

Cited by 14 publications

References 45 publications

Molecular mechanism of CCDC106 regulating the p53-Mdm2/MdmX signal axis

Molecular mechanism of CCDC106 regulating the p53-Mdm2/MdmX signal axis

Genomic analysis of cervical carcinoma identifies Alpelisib as a therapeutic option for PIK3CA‐mutant cervical carcinoma via the PI3K/AKT pathway

Human papillomavirus associated cervical lesion: pathogenesis and therapeutic interventions

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