Purpose: The p73 gene produces different protein isoforms using alternative promoters and splicing, which have different biological characteristics. This study was to investigate the expression patterns of two distinct p73 isoforms (DNp73 and TAp73a) in cervical squamous cell carcinomas (SCC) and the relationship between their expressions and prognostic significance in cervical SCC patients. Experimental Design: We investigated the protein expressions of DNp73 and TAp73a in 117 cervical SCC and 113 normal cervical tissues using immunohistochemistry. The expression levels were analyzed with clinical variables and patients' survival. Results: DNp73and TAp73a were significantly overexpressed in cervical SCC compared with those in normal cervical epithelium (P < 0.001). However, their expressions were inversely correlated (P < 0.001, R = À0.368) and associated with differential tumor radiosensitivity. Overexpression of DNp73 was significantly found in SCC resistant to irradiation (P < 0.001), whereas increase of TAp73a expression was observed in the majority of SCC sensitive to irradiation (P < 0.001). Multivariate and survival analyses indicated that the expressions of DNp73 and TAp73a were independently associated with prognosis: DNp73 was associated with recurrence of the disease [P = 0.001; odds ratio (OR), 4.857] and an adverse outcome (P = 0.012; OR, 4.676), whereasTAp73a predicted a better survival of cervical SCC patients (P = 0.018; OR, 0.065). Conclusions:The p73 gene might be an important determinant of cellular response to irradiation. The expressions of the two main isoforms (DNp73 and TAp73a) might be potential markers for predicting the prognosis and sensitivity to radiotherapy in patients with cervical SCC.

Radiation therapy is the most effective therapy for cervical cancer in advanced stages. p53 plays a critical role in the cellular response to radiation-induced DNA damage. However, p53 function is often impaired in the presence of the oncoprotein E6 from human papillomavirus, which is often associated with the development of cervical cancer. p73, a p53 family member, is highly similar to p53, but is resistant to the degradation by human papillomavirus E6. In this study, we investigated the role of p73A in relation to cellular radiosensitivity in the p53-impaired cervical cancer cells. Radiosensitivity and irradiation-induced apoptotic cell death were examined in the exogenous overexpressed p73A-and p53-impaired cells. Our results showed that the endogenous p73A expressed only in the radiosensitive cervical cancer C4-1

Background:The purpose of this study was to characterise the oncogenic roles of C35, a novel protein binding partner of ΔNp73, in ovarian cancer and to investigate the functional significance of C35–ΔNp73 interaction in the regulation of chemo-resistance.Methods:C35 expression was evaluated by quantitative real-time PCR in human ovarian cancer tissues and cell lines. The aggressiveness of ovarian cancer cells overexpressing C35 was examined by cell proliferation, migration, soft agar and nude mouse xenograft. The significance of C35–ΔNp73 interaction in chemo-resistance was evaluated by apoptosis assays and cell viability after cisplatin treatment.Results:The expression of C35 was significantly enhanced in human ovarian cancer tissues. Overexpression of C35 augmented proliferation, migration and tumourigenicity in ovarian cancer cell lines. C35 knockdown inhibited cell motility and cell growth. The co-expression of C35 and ΔNp73 by transient or stable transfection in ovarian cancer cells induced greater resistance to cisplatin treatment than did transfection with C35 or ΔNp73 alone. The cisplatin resistance was demonstrated to be caused by increased AKT and NFκB activity induced by C35–ΔNp73.Conclusion:Our results suggest that ΔNp73 might cooperate with C35 to promote tumour progression and contribute to cisplatin resistance in ovarian cancer cells. Future studies of the functional roles of ΔNp73 and C35 will provide insight that will aid in the establishment of new strategies and more effective therapies.

E2 protein binding to the four E2 binding sites (E2BSs) at the long control region of Human Papillomavirus (HPV) 16/18 genome may exert either transcriptional activation/repression on E6 and E7 oncoproteins. Methylation status at the E2BSs may affect the relative binding of E2 protein to them. In this study, methylation percentage at E2BS 1, 2 (promoter-proximal), and 4 (promoter-distal) were assessed by pyrosequencing and compared among HPV 16/18-positive cervical cancer, high-grade, and low-grade Cervical Intraepithelial Neoplasia, Atypical Squamous Cells of Undetermined Significance, and normal cervical epithelium. HPV 16 E2BS1&2 were more methylated than HPV 16 E2BS4 in cervical cancer whereas in cervical premalignant lesions and normal epithelium, HPV 16 E2BS1&2 were less methylated than HPV 16 E2BS4. HPV 18 E2BS1&2 remained more methylated than E2BS4 in all histological groups. HPV 16 E2BS1&2 methylation increased from high-grade lesions to cervical cancer (P < 0.001). HPV 16 E2BS4 methylation increased from low-grade to high-grade premalignant lesions (P = 0.041). Both HPV 18 E2BS1&2 and E2BS4 methylation increased from low-grade to high-grade Cervical Intraepithelial Neoplasia (P = 0.019 and 0.001 respectively) and further increased form high-grade lesions to cervical cancer (P < 0.001 and 0.005 respectively). Conclusively, HPV 16 E2BS1&2 (for transcriptional repression of E6/E7 oncoproteins) became more heavily methylated than E2BS4 (for transcriptional activation of E6/E7) in cervical cancer, favouring the differential binding of E2 protein to E2BS4. Increasing methylation at HPV 16/18 E2BSs are potentially useful adjunctive molecular markers for predicting progression from low-grade to high-grade cervical premalignant lesions and from high-grade lesions to cervical cancer.

Objectives Cancer stem cells (CSCs) are a subpopulation of cancer cells that share similarities with somatic stem cells. CSCs are believed to play a key role in carcinogenesis, metastasis, cancer relapse, and drug resistance. Despite their significant impacts, the specific biological markers for the identification of CSCs and their differentiation/transformation mechanisms have not yet been fully characterized. Methods Utilizing stem cell markers, the ability to differentiate in multiple directions, and resistance to radiotherapy and chemotherapy, CSCs were identified. To assess the variations in gene expression, gene alterations, protein expression, and cell proliferation between CSCs and U118MG glioma cells, second generation sequencing, Real-Time PCR, Western Blotting, and CCK-8 were employed. Results In this study, we identified a subset of CSCs in human U118MG glioma cells that expressed the stem cell biomarkers CD133+, OCT4+, and CD44+. These cells exhibited stem cell-like characteristics such as multilineage differentiation and resistance to chemical and radiation stresses. Notably, they can form neurons with electrical signals and sodium currents. Further study also revealed that the malignant growth of this CSC subset was controlled by long noncoding RNA (Lnc-DC) through the STAT3 pathway. Conclusions As a potential therapeutic approach, inhibiting Lnc-DC may be beneficial in hindering carcinogenesis and drug resistance, as it selectively targets the growth of CSCs.