TEX10 Promotes the Tumorigenesis and Radiotherapy Resistance of Urinary Bladder Carcinoma by Stabilizing XRCC6

Urinary bladder carcinoma refers to the commonest carcinoma with weak prognostic result for the patient as impacted by the limited treatment possibilities and challenging diagnosing process. Nevertheless, the molecular underpinning of bladder carcinoma malignant progression is still not clear. As a novel core part of pluripotency circuitry, testicular expression 10 (TEX10) plays an actively noticeable effect on reprogramming, early embryo development, and embryonic stem cell self-renewal. Nevertheless, TEX10 expressions and functions within bladder carcinoma are still not known. The present work is aimed at revealing TEX10 expression and biological function within urinary bladder carcinoma and elucidating the potential mechanisms. Results showed that TEX10 is abundant in urinary bladder carcinoma, and its protein level was related to poor disease-free survival in a positive manner. Reduced TEX10 level inhibited urinary bladder carcinoma cell proliferating process and metastasis in vitro and xenograft tumorigenicity in vivo. Notably, TEX10 might regulate carcinoma cell proliferating process and metastasis via XRCC6, thereby controlling the signaling of Wnt/β-catenin and DNA repair channel. Moreover, TEX10 gene knockout reduced the radiotherapy resistance of urinary bladder carcinoma. In brief, this work revealed that TEX10 could exert a significant carcinogenic effect on urinary bladder carcinoma tumorigenesis and radiotherapy resistance through the activation of XRCC6-related channels. Accordingly, targeting TEX10 is likely to offer a novel and feasible therapeutically related strategy for inhibiting urinary bladder carcinoma tumorigenicity.

The Molecular Roles and Clinical Implications of Non-Coding RNAs in Gastric Cancer

Gastric cancer (GC) is one of the most common malignancies in the world. It is also the fifth most common cancer in China. In recent years, a large number of studies have proved that non-coding RNAs (ncRNAs) can regulate cell proliferation, invasion, metastasis, apoptosis, and angiogenesis. NcRNAs also influence the therapeutic resistance of gastric cancer. NcRNAs mainly consist of miRNAs, lncRNAs and circRNAs. In this paper, we summarized ncRNAs as biomarkers and therapeutic targets for gastric cancer, and also reviewed their role in clinical trials and diagnosis. We sum up different ncRNAs and related moleculars and signaling pathway in gastric cancer, like Bcl-2, PTEN, Wnt signaling. In addition, the potential clinical application of ncRNAs in overcoming chemotherapy and radiotherapy resistance in GC in the future were also focused on.

The long non-coding RNA HOTAIRM1 promotes tumor aggressiveness and radiotherapy resistance in glioblastoma

Glioblastoma is the most common malignant primary brain tumor. To date, clinically relevant biomarkers are restricted to isocitrate dehydrogenase (IDH) gene 1 or 2 mutations and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Long non-coding RNAs (lncRNAs) have been shown to contribute to glioblastoma pathogenesis and could potentially serve as novel biomarkers. The clinical significance of HOXA Transcript Antisense RNA, Myeloid-Specific 1 (HOTAIRM1) was determined by analyzing HOTAIRM1 in multiple glioblastoma gene expression data sets for associations with prognosis, as well as, IDH mutation and MGMT promoter methylation status. Finally, the role of HOTAIRM1 in glioblastoma biology and radiotherapy resistance was characterized in vitro and in vivo. We identified HOTAIRM1 as a candidate lncRNA whose up-regulation is significantly associated with shorter survival of glioblastoma patients, independent from IDH mutation and MGMT promoter methylation. Glioblastoma cell line models uniformly showed reduced cell viability, decreased invasive growth and diminished colony formation capacity upon HOTAIRM1 down-regulation. Integrated proteogenomic analyses revealed impaired mitochondrial function and determination of reactive oxygen species (ROS) levels confirmed increased ROS levels upon HOTAIRM1 knock-down. HOTAIRM1 knock-down decreased expression of transglutaminase 2 (TGM2), a candidate protein implicated in mitochondrial function, and knock-down of TGM2 mimicked the phenotype of HOTAIRM1 down-regulation in glioblastoma cells. Moreover, HOTAIRM1 modulates radiosensitivity of glioblastoma cells both in vitro and in vivo. Our data support a role for HOTAIRM1 as a driver of biological aggressiveness, radioresistance and poor outcome in glioblastoma. Targeting HOTAIRM1 may be a promising new therapeutic approach.

Reversal of Radiotherapy Resistance of Ovarian Cancer Cell Strain CAOV3/R by Targeting lncRNA CRNDE

Radiotherapy resistance is one of the key factors of poor prognosis of ovarian cancer clinical treatment. The search for key targets of ovarian cancer radiotherapy resistance has become a high priority. Long noncoding RNA plays an important role in tumor development. However, the key lncRNA in ovarian cancer radiotherapy resistance is not identified. Our finding that lncRNA CRNDE is highly expressed in the radiotherapy resistance cell line CAOV3/R drew our attention. Therefore, in this study, we targeted lncRNA CRNDE to analyze whether it is a key factor of radiotherapy resistance in ovarian cancer. Ultimately, we found that silencing lncRNA CRNDE could reverse CAOV3/R radiotherapy resistance, which would be a boon to clinical treatment.

Natural Small Molecules Targeting NF-κB Signaling in Glioblastoma

Nuclear factor-κB (NF-κB) is a transcription factor that regulates various genes that mediate various cellular activities, including propagation, differentiation, motility, and survival. Abnormal activation of NF-κB is a common incidence in several cancers. Glioblastoma multiforme (GBM) is the most aggressive brain cancer described by high cellular heterogeneity and almost unavoidable relapse following surgery and resistance to traditional therapy. In GBM, NF-κB is abnormally activated by various stimuli. Its function has been associated with different processes, including regulation of cancer cells with stem-like phenotypes, invasion of cancer cells, and radiotherapy resistance identification of mesenchymal cells. Even though multimodal therapeutic approaches such as surgery, radiation therapy, and chemotherapeutic drugs are used for treating GBM, however; the estimated mortality rate for GBM patients is around 1 year. Therefore, it is necessary to find out new therapeutic approaches for treating GBM. Many studies are focusing on therapeutics having less adverse effects owing to the failure of conventional chemotherapy and targeted agents. Several studies of compounds suggested the involvement of NF-κB signaling pathways in the growth and development of a tumor and GBM cell apoptosis. In this review, we highlight the involvement of NF-κB signaling in the molecular understanding of GBM and natural compounds targeting NF-κB signaling.

Identification of Biomarkers for Cervical Cancer Radiotherapy Resistance Based on RNA Sequencing Data

Cervical cancer as a common gynecological malignancy threatens the health and lives of women. Resistance to radiotherapy is the primary cause of treatment failure and is mainly related to difference in the inherent vulnerability of tumors after radiotherapy. Here, we investigated signature genes associated with poor response to radiotherapy by analyzing an independent cervical cancer dataset from the Gene Expression Omnibus, including pre-irradiation and mid-irradiation information. A total of 316 differentially expressed genes were significantly identified. The correlations between these genes were investigated through the Pearson correlation analysis. Subsequently, random forest model was used in determining cancer-related genes, and all genes were ranked by random forest scoring. The top 30 candidate genes were selected for uncovering their biological functions. Functional enrichment analysis revealed that the biological functions chiefly enriched in tumor immune responses, such as cellular defense response, negative regulation of immune system process, T cell activation, neutrophil activation involved in immune response, regulation of antigen processing and presentation, and peptidyl-tyrosine autophosphorylation. Finally, the top 30 genes were screened and analyzed through literature verification. After validation, 10 genes (KLRK1, LCK, KIF20A, CD247, FASLG, CD163, ZAP70, CD8B, ZNF683, and F10) were to our objective. Overall, the present research confirmed that integrated bioinformatics methods can contribute to the understanding of the molecular mechanisms and potential therapeutic targets underlying radiotherapy resistance in cervical cancer.

NOX4 Signaling Mediates Cancer Development and Therapeutic Resistance through HER3 in Ovarian Cancer Cells

Development of resistance to therapy in ovarian cancer is a major hinderance for therapeutic efficacy; however, new mechanisms of the resistance remain to be elucidated. NADPH oxidase 4 (NOX4) is responsible for higher NADPH activity to increase reactive oxygen species (ROS) production. In this study, we showed that higher levels of NOX4 were detected in a large portion of human ovarian cancer samples. To understand the molecular mechanism of the NOX4 upregulation, we showed that NOX4 expression was induced by HIF-1α and growth factor such as IGF-1. Furthermore, our results indicated that NOX4 played a pivotal role in chemotherapy and radiotherapy resistance in ovarian cancer cells. We also demonstrated that NOX4 knockdown increased sensitivity of targeted therapy and radiotherapy through decreased expression of HER3 (ERBB3) and NF-κB p65. Taken together, we identified a new HIF-1α/NOX4 signal pathway which induced drug and radiation resistance in ovarian cancer. The finding may provide a new option to overcome the therapeutic resistance of ovarian cancer in the future.