POLR2J expression promotes glioblastoma malignancy by regulating oxidative stress and the STAT3 signaling pathway.

Glioblastoma is the most common cancer in the brain, resistant to conventional therapy and prone to recurrence. Therefore, it is crucial to explore novel therapeutics strategies for the treatment and prognosis of GBM. In this study, through analyzing online datasets, we elucidated the expression and prognostic value of POLR2J and its co-expressed genes in GBM patients. Functional experiments, including assays for cell apoptosis and cell migration, were used to explore the effects of POLR2J and vorinostat on the proliferation and migration of GBM cells. The highest overexpression of POLR2J, among all cancer types, was observed in GBM. Furthermore, high expression of POLR2J or its co-expressed genes predicted a poor outcome in GBM patients. DNA replication pathways were significantly enriched in the GBM clinical samples with high POLR2J expression, and POLR2J suppression inhibited proliferation and triggered cell cycle G1/S phase arrest in GBM cells. Moreover, POLR2J silencing activated the unfolded protein response (UPR) and significantly enhanced the anti-GBM activity of vorinostat by suppressing cell proliferation and inducing apoptosis. Additionally, POLR2J could interact with STAT3 to promote the metastatic potential of GBM cells. Our study identifies POLR2J as a novel oncogene in GBM progression and provides a promising strategy for the chemotherapeutic treatment of GBM.

Recent research progress of circular RNAs in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is an extremely heterogeneous malignant tumor with a high morbidity and mortality. Circular RNAs (circRNAs) are noncoding RNAs with high stability, organ/tissue/cell-specific expression and are conserved across species. Accumulating evidence suggested that circRNAs play crucial roles as microRNA sponges, protein sponges, scaffolds, recruiters and could even polypeptide encoders. Many studies have since revealed that circRNAs were aberrantly expressed in HCC and acted as crucial modulators of HCC carcinogenesis and progression. Furthermore, circRNAs have also been identified as potential diagnostic and prognostic biomarkers for HCC. In this review, we thoroughly outline and evaluate the function of circRNAs in HCC development, with an emphasis on the specific molecular pathways by which they participated in the formation and progression of HCC, and we address their potential for serving as clinical biomarkers in HCC.

DYRK1A suppression attenuates HIF­1α accumulation and enhances the anti­liver cancer effects of regorafenib and sorafenib under hypoxic conditions.

Hypoxia promotes drug resistance and induces the expression of hypoxia inducible factor (HIF)­1α in liver cancer cells. However, to date, no selective HIF­1α inhibitor has been clinically approved. The aim of this study is to investigate a drug­targetable molecule that can regulate HIF­1α under hypoxia. The present study demonstrated that hyperactivation of dual­specificity tyrosine­phosphorylation­regulated kinase 1A (DYRK1A)/HIF­1α signaling was associated with an increased risk of liver cancer. In addition, DYRK1A knockdown using small interfering RNA transfection or treatment with harmine, a natural alkaloid, significantly reduced the protein expression levels of HIF­1α in liver cancer cells under hypoxic conditions in vitro. Conversely, DYRK1A overexpression­vector transfection in liver cancer cell lines notably induced HIF­1α expression under the same conditions. Furthermore, DYRK1A was shown to interact and activate STAT3 under hypoxia to regulate HIF­1α expression. These findings indicated that DYRK1A may be a potential upstream activator of HIF­1α and positively regulate HIF­1α via the STAT3 signaling pathway in liver cancer cells. Additionally, treatment with harmine attenuated the proliferative ability of liver cancer cells under hypoxic conditions using sulforhodamine B and colony formation assay. Furthermore, DYRK1A knockdown could significantly enhance the anti­liver cancer effects of regorafenib and sorafenib under hypoxia. Co­treatment with harmine and either regorafenib or sorafenib also promoted cell death via the STAT3/HIF­1α/AKT signaling pathway under hypoxia using PI staining and western blotting. Overall, the results from the present study suggested that DYRK1A/HIF­1α signaling may be considered a novel pathway involved in chemoresistance, thus providing a potentially effective therapeutic regimen for treating liver cancer.

Harmine reinforces the effects of regorafenib on suppressing cell proliferation and inducing apoptosis in liver cancer cells.

The overall outcomes for patients with advanced liver cancer are far from satisfactory, and the development of more effective therapeutic strategies for liver cancer is required. Sulforhodamine blue and colony formation assays were performed to detect the proliferation of liver certain cancer cells, including HepG2 and Hep3B. Western blotting was also preformed to detect the expression of indicated proteins, including cleaved-caspase-3, cleaved-poly (ADP-ribose) polymerase, dual-specificity tyrosine phosphorylation kinase 1A (DYRK1A), PARP-1/2, GAPDH, myeloid cell leukemia-1, phosphorylated-AKT (Ser473), caspase-3, α-tubulin and AKT. PI staining was used to detect cell death. In the present study, DYRK1A knockdown significantly enhanced the anti-liver cancer effect of regorafenib in vitro. Furthermore, DYRK1A inhibitor harmine together with regorafenib provided synergistic anti-liver cancer activity by suppressing cell proliferation. In addition, harmine significantly enhanced regorafenib-induced cell death in liver cancer cells. It has been reported that AKT signaling is activated in regorafenib-resistant cancer cells and plays a crucial role in the regulation of cellular sensitivity to regorafenib. In the present study, AKT was activated in regorafenib-treated cells, and harmine could suppress the activation of AKT and reinforce the anti-cancer effects of regorafenib via regulating AKT in liver cancer cells. These data indicated that harmine enhanced the anti-cancer effects of regorafenib on suppressing cell proliferation and inducing apoptosis in liver cancer cells via regulating the activation of AKT, and harmine plus regorafenib may be a potential therapeutic regimen for treating patients with liver cancer.

Strong Visible Light Absorption and Abundant Hotspots in Au-Decorated WO3 Nanobricks for Efficient SERS and Photocatalysis.

Metal/semiconductor hybrids show potential application in fields of surface-enhanced Raman spectroscopy (SERS) and photocatalysis due to their excellent light absorption, electric field, and charge-transfer properties. Herein, a WO3-Au metal/semiconductor hybrid, which was a WO3 nanobrick decorated with Au nanoparticles, was prepared via a facile hydrothermal method. The WO3-Au hybrids show excellent visible light absorption, strong plasmon coupling, high-performance SERS, and good photocatalytic activity. In particular, on sensing rhodamine B (RhB) under 532 nm excitation, bare WO3 nanobricks have a Raman enhancement factor of 2.0 × 106 and a limit of detection of 10-8 M due to the charger-transfer property and abundant oxygen vacancies. WO3-Au metal/semiconductor hybrids display a largely improved Raman enhancement factor compared to pure Au and WO3 components owing to the synergistic effect of electromagnetic enhancement and charge transfer. The Raman enhancement factor and limit of detection are further improved, reaching 5.3 × 108 and 10-12 M, respectively, on increasing the content of Au to 2.1 wt %, owing to the strong plasmon coupling between the Au nanoparticles. Additionally, the WO3-Au hybrids also exhibit excellent photocatalytic activity toward degradation of RhB under visible light irradiation. WO3-Au (2.1 wt %) possesses the fastest photocatalytic rate, which is 6.1 and 2.0 times that of pure WO3 nanobricks and commercial P25, respectively. The enhanced photocatalytic activity is attributed to the strong plasmon coupling and the efficient charge transfer between Au and WO3 nanobricks. The as-prepared materials show great potential in detecting and degrading pollutants in environmental treatment.