Endometrial cancer is one of the most common gynaecological cancers in developed countries. Its incidence has increased 20% over the last decade and the death rate has increased >100% over the past two decades. Current models for prediction of prognosis and treatment response are suboptimal, and as such biomarkers to support clinical decision-making and contribute to individualised treatment are needed. In this study, we show that the E3-ubiquitin ligase PIR2/RNF144B is a potential targetable biomarker in endometrial cancer. At transcript level, it is expressed both in normal endometrium and tumour samples, but at protein level, it is expressed in tumours only. By using endometrial cancer cell lines, we demonstrated that PIR2/RNF144B is stabilised via phosphorylation downstream of GSK3β and this is necessary for the proliferation of endometrial cancer cells, in the absence of oestrogenic growth stimuli. Here, inactivation of GSK3β activity is associated with loss of PIR2/RNF144B protein and consequent inhibition of cell proliferation. Our results, therefore, substantiate PIR2/RNF144B as a novel candidate for targeted therapy in endometrial cancer.
Cervical cancer is the third most common malignancy diagnosed in women worldwide. The major aetiological factor underlying the malignant transformation of cervical cells is the persistent infection with high-risk human papillomaviruses (HR-HPV), with more than 99% of cases expressing viral sequences. Here, we report a previously unknown mechanism driven by high-risk human papillomavirus E7 protein to modulate response to DNA damage in cervical cancer cells. Our data shows that HR-HPV E7 oncoprotein induces the transcription of the p53-family member p63, which modulates DNA damage response pathways, to facilitate repair of DNA damage. Based on our findings, we proposed a model, where HR-HPV could interfere with the sensitivity of transformed cells to radiation therapy by modulating DNA damage repair efficiency. Importantly, we have shown for the first time a critical role for p63 in response to DNA damage in cervical cancer cells.
IntroductionIn Saudi Arabia, limited studies have evaluated factors including epidemiologic, clinical, and laboratory findings that are associated with COVID-19 disease. The aim of this paper was to identify laboratory parameters used in King Abdulaziz University Hospital which show an association with disease severity and patient outcome in the form of mortality.MethodsAge, gender, medical history, and laboratory parameters were all retrospectively assessed concerning disease severity and disease outcome in a total of 111 COVID-19 patients at King Abdulaziz University Hospital between July 2020 and August 2020. Patients were categorized into mild disease if they did not require ward admission, moderate if they met the Ministry of Health criteria for isolation ward admition, and severe if they were admitted to the ICU.ResultsAge but not gender was associated with the disease severity X2 (4, N = 110) = 27.2, p <0.001. Of all laboratory parameters on admission, only the levels of Albumin appeared to be significantly associated X2 (2, N =70) = 6.6, p <0.05 with disease severity. Age but not gender was also significantly associated with disease outcome X2 (2, N = 110) = 12.8, p < 0.01. Interestingly, RBC count also showed a significant relation with disease outcome X2 (2, N = 71) = 6.1, p <0.05.DiscussionThis study provides more understanding of the laboratory characteristics in our part of the world to efficiently manage the disease.
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