Colorectal carcinoma (CRC) is a malignant epithelial tumour with tremendous invasion and metastatic capacity. Transforming acidic coiled-coil protein-3 (TACC3), a frequently aberrantly expressed oncogene, is an important biomarker in various human cancers. Our study aimed to investigate the expression and function of TACC3 in human CRC. We found that TACC3 was over-expressed at both the mRNA and protein levels in CRC cells and in biopsies of CRC tissues compared with normal controls as determined by qRT-PCR, western blot and immunohistochemical (IHC) staining assays. IHC staining of samples from 161 patients with CRC also revealed that TACC3 expression was significantly correlated with clinical stage (P = 0.045), T classification (P = 0.029) and M classification (P = 0.020). Multivariate analysis indicated that high TACC3 expression was an independent prognostic marker for CRC. Patients who had high TACC3 expression had significantly poorer overall survival (OS, P = 0.023) and disease-free survival (DFS, P = 0.019) compared to patients who had low TACC3 expression. Furthermore, TACC3 knockdown attenuated CRC cell proliferation, colony formation capability, migration and invasion capability, and tumourigenesis in nude mice; these properties were measured using a real-time cell analyser (RTCA), clonogenicity analysis, and transwell and xenograft assays, respectively. These data indicate that TACC3 promotes CRC progression and could be an independent prognostic factor and a potential therapeutic target for CRC.

c-Fos is a major component of activator protein (AP)-1 complex. It has been implicated in cell differentiation, proliferation, angiogenesis, invasion, and metastasis. To investigate the role of c-Fos in glioma radiosensitivity and to understand the underlying molecular mechanisms, we downregulated c-Fos gene expression by lentivirus-mediated shRNA in glioma cell lines and subsequently analyzed the radiosensitivity, DNA damage repair capacity, and cell cycle distribution. Finally, we explored its prognostic value in 41 malignant glioma patients by immunohistochemistry. Our results showed that silencing c-Fos sensitized glioma cells to radiation by increasing radiation-induced DNA double strand breaks (DSBs), disturbing the DNA damage repair process, promoting G2/M cell cycle arrest, and enhancing apoptosis. c-Fos protein overexpression correlated with poor prognosis in malignant glioma patients treated with standard therapy. Our findings provide new insights into the mechanism of radioresistance in malignant glioma and identify c-Fos as a potentially novel therapeutic target for malignant glioma patients.

Radioresistance‐induced residual and recurrent tumours are the main cause of treatment failure in nasopharyngeal carcinoma (NPC). Thus, the mechanisms of NPC radioresistance and predictive markers of NPC prognosis and radioresistance need to be investigated and identified. In this study, we identified RPA3 as a candidate radioresistance marker using RNA‐seq of NPC samples. In vitro studies further confirmed that RPA3 affected the radiosensitivity of NPC cells. Specifically, the overexpression of RPA3 enhanced radioresistance and the capacity for DNA repair of NPC cells, whereas inhibiting RPA3 expression sensitized NPC cells to irradiation and decreased the DNA repair capacity. Furthermore, the overexpression of RPA3 enhanced RAD51 foci formation in NPC cells after irradiation. Immunohistochemical assays in 104 NPC specimens and 21 normal epithelium specimens indicated that RPA3 was significantly up‐regulated in NPC tissues, and a log‐rank test suggested that in patients with NPC, high RPA3 expression was associated with shorter overall survival (OS) and a higher recurrence rate compared with low expression (5‐year OS rates: 67.2% versus 86.2%; 5‐year recurrence rates: 14.8% versus 2.3%). Moreover, TCGA data also indicated that high RPA3 expression correlated with poor OS and a high recurrence rate in patients with head and neck squamous cell carcinoma (HNSC) after radiotherapy. Taken together, the results of our study demonstrated that RPA3 regulated the radiosensitivity and DNA repair capacity of NPC cells. Thus, RPA3 may serve as a new predictive biomarker for NPC prognosis and radioresistance to help guide the diagnosis and individualized treatment of patients with NPC.

BackgroundBRCC3 has been found to be aberrantly expressed in breast tumors and involved in DNA damage response. The contribution of BRCC3 to nasopharyngeal carcinoma prognosis and radiosensitivity is still unclear.MethodsImmunohistochemical analysis of BRCC3 was carried out in 100 nasopharyngeal carcinoma tissues, and the protein level was correlated to patient survival. BRCC3 expression of nasopharyngeal carcinoma cell lines was determined by Western-blotting and real-time PCR. Additionally, the effects of BRCC3 knockdown on nasopharyngeal carcinoma cell clongenic survival, DNA damage repair, and cell cycle distribution after irradiation was assessed.ResultsThe BRCC3 protein level was inversely correlated with nasopharyngeal carcinoma patient overall survival (P < 0.001) and 3-year loco-regional relapse-free survival (P = 0.034). Multivariate analysis demonstrated that BRCC3 expression was an independent prognostic factor (P = 0.010). The expression of BRCC3 was much higher in radioresistant nasopharyngeal carcinoma cells than in radiosensitive cells. Knockdown of BRCC3 increased the cell survival fraction, attenuated DNA damage repair and resulted in G2/M cell cycle arrest in radioresistant NPC cells.ConclusionsHigh BRCC3 expression in nasopharyngeal carcinoma patients is associated with poor survival. BRCC3 knockdown could abate the radioresistance in nasopharyngeal carcinoma cells. These findings suggest the utility of BRCC3 as a prognostic biomarker and novel target for nasopharyngeal carcinoma.

Integrin α6 emerges as an attractive cancer therapeutic target. Here, the authors present for the first-time, that integrin α6 is overexpressed in nasopharyngeal carcinoma (NPC) and serves as a prognostic predictor and a cancer stem cell (CSC) biomarker. An NPC-targeted peptide CRWYDENAC (dubbed RWY) with high specificity and affinity for integrin α6 is identified, and an integrin α6-targeted nanotherapeutic against NPC is developed by encapsulating a cisplatin prodrug Pt(IV) with RWY-grafted polymeric nanoparticles (dubbed RWY-NP/Pt(IV)). The delivery of cisplatin prodrug Pt(IV) by RWY-NP/Pt(IV) results in an approximately 100-fold increase in cytotoxicity over free cisplatin, as well as a 5-fold increase over Scramble-NP/Pt(IV) control. RWY-NP/Pt(IV) suppresses NPC tumor growth with an inhibition rate of around 78%, compared with the 44% and 41% achieved by free cisplatin and Scramble-NP/Pt(IV) treatment. Loss of body weight is observed in free cisplatin treated mice but not in RWY-NP/Pt(IV)treated mice. Taken together, RWY-NP/Pt(IV) enhances the therapeutic efficacy of cisplatin treatment and reduces deleterious side effects, suggesting the potential application of the integrin α6-targeted RWY peptide for nanotherapeutics against NPC.