Jin Bai

p53-mediated autophagic regulation: A prospective strategy for cancer therapy

Autophagy is a major catabolic process that degrades and recycles cytosolic components in autophagosomes, which fuse with lysosomes. This process enables starving cells to sustain their energy requirements and metabolic states, thus facilitating their survival, especially in cancer pathogenesis. The regulation of autophagy is quite intricate. It involves a series of signaling cascades including p53, known as the best-characterized tumor suppressor protein. Recent reports have indicated that p53 plays dual roles in regulating autophagy depending on its subcellular localization. Nuclear p53 facilitates autophagy by transactivating its target genes, whereas cytoplasmic p53 mainly inhibits autophagy through extranuclear, transcription-independent mechanisms. The relationship between autophagy and neoplasia is complicated. It may be intrinsically associated with the functional status of p53, but this is not clearly elucidated. This review focuses on the role of p53 as a master regulator of autophagy. We conclude that the contextual role of autophagy in cancer, which could be switched by p53 status, is expected to be developed into a new anticancer therapeutic approach.

BRG1 is a prognostic marker and potential therapeutic target in human breast cancer.

BRG1, a core component of the SWI/SNF chromatin-remodeling complex, has been implicated in cancer development; however, the biological significance of BRG1 in breast cancer remains unknown. We explored the role of BRG1 in human breast cancer pathogenesis. Using tissue microarray and immunohistochemistry, we evaluated BRG1 staining in 437 breast cancer specimens and investigated its role in breast cancer cell proliferation, migration and invasion. Our Kaplan-Meier survival curves showed that high BRG1 expression is inversely correlated with both overall (P = 0.000) and disease-specific (P = 0.000) 5-year patient survival. Furthermore, we found that knockdown of BRG1 by RNA interference markedly inhibits cell proliferation and causes cessation of cell cycle. This reduced cell proliferation is due to G1 phase arrest as cyclin D1 and cyclin E are diminished whereas p27 is upregulated. Moreover, BRG1 depletion induces the expression of TIMP-2 but reduces MMP-2, thereby inhibiting the ability of cells to migrate and to invade. These results highlight the importance of BRG1 in breast cancer pathogenesis and BRG1 may serve as a prognostic marker as well as a potentially selective therapeutic target.

RUNX3 Suppresses Migration, Invasion and Angiogenesis of Human Renal Cell Carcinoma

RUNX3 (runt-related transcription factor-3) is a known tumor suppressor gene which exhibits potent antitumor activity in several carcinomas. However, little is known about the role of RUNX3 in human renal cell carcinoma (RCC). To investigate the clinical relevance of RUNX3 in RCC patients, immunohistochemistry was performed to detect the clinical relevance of RUNX3 in 75 RCC tissues and paired non-cancerous tissues by using tissue microarray (TMA). We also investigated the role of RUNX3 in RCC cell migration, invasion and angiogenesis. The RUNX3 expression was decreased dramatically in human RCC tissue. The RUNX3 expression was significantly correlated with tumor size (P<0.001), depth of invasion (P<0.001), and of TNM stage (P<0.001). Restoration of RUNX3 significantly decreased renal carcinoma cell migration and invasion capacity compared with controls. In addition, we found that overexpression of RUNX3 reduced the proliferation and tube formation of human umbilical vascular endothelial cells (HUVECs). Gelatin zymography and Western blot showed that RUNX3 expression suppressed matrix metalloproteinase-9 (MMP-9) protein level and enzyme activity. Western blot and ELISA showed that RUNX3 restoration inhibited the expression and secretion of vascular endothelial growth factor (VEGF). Taken together, our studies indicate that decreased expression of RUNX3 in human RCC tissue is significantly correlated with RCC progression. Restoration of RUNX3 expression significantly inhibits RCC cells migration, invasion and angiogenesis. These findings provide new insights into the significance of RUNX3 in migration, invasion and angiogenesis of RCC.

Rap2B promotes proliferation, migration, and invasion of human breast cancer through calcium-related ERK1/2 signaling pathway

Rap2B, a member of GTP-binding proteins, is widely upregulated in many types of tumors and promotes migration and invasion of human suprarenal epithelioma. However, the function of Rap2B in breast cancer is unknown. Expression of Rap2B was examined in breast cancer cell lines and human normal breast cell line using Western blot analysis. Using the CCK-8 cell proliferation assay, cell cycle analysis, and transwell migration assay, we also elucidated the role of Rap2B in breast cancer cell proliferation, migration, and invasion. Results showed that the expression of Rap2B is higher in tumor cells than in normal cells. Flow cytometry and Western blot analysis revealed that Rap2B elevates the intracellular calcium level and further promotes extracellular signal-related kinase (ERK) 1/2 phosphorylation. By contrast, calcium chelator BAPTM/AM and MEK inhibitor (U0126) can reverse Rap2B-induced ERK1/2 phosphorylation. Furthermore, Rap2B knockdown inhibits cell proliferation, migration, and invasion abilities via calcium related-ERK1/2 signaling. In addition, overexpression of Rap2B promotes cell proliferation, migration and invasion abilities, which could be neutralized by BAPTM/AM and U0126. Taken together, these findings shed light on Rap2B as a therapeutic target for breast cancer.

Synthesis and properties of visible light responsive g-C3N4/Bi2O2CO3 layered heterojunction nanocomposites

Visible light responsive g-C3N4/Bi2O2CO3 layered heterojunction nanocomposites were prepared by two methods, self-assembly and chemical precipitation. X-ray diffraction (XRD), UV-Vis spectroscopy, N2 adsorption, Scanning electron microscopy (SEM), electrochemical impedance spectra (EIS) and X-ray photoelectron spectroscopy (XPS) were used to characterize the prepared catalysts. The results indicated that the preparation method does not influence the crystal phase, morphology and optical property of the obtained nanocomposites, but affects the interaction strength between g-C3N4 and Bi2O2CO3, leading to an obvious difference in the separation rate of photogenerated electrons and holes. The activities were tested in photocatalytic rhodamine B (RhB) and phenol degradation under visible light. The g-C3N4/Bi2O2CO3 nanocomposite with a stronger interaction showed the better activity. The ˙O2− radicals are responsible for the degradation of RhB. No obvious decrease in activity was observed for g-C3N4/Bi2O2CO3 nanocomposites prepared by the self-assembly method after three cycles. The significant enhancement of the photocatalytic activity was attributed to the high charge-separation efficiency due to the hybrid effect of RhB, Bi2O2CO3 and g-C3N4. The self assembly method assisted by CTAB leads to tight decoration of Bi2O2CO3 nanoparticles on g-C3N4 sheets facilitating intimate contact and formation of a stable heterojunction.

PinX1 inhibits the invasion and metastasis of human breast cancer via suppressing NF-κB/MMP-9 signaling pathway

BackgroundPinX1 (PIN2/TRF1-interacting telomerase inhibitor 1) was suggested to be correlated with tumor progression. This study was designed to evaluate the role of PinX1 in human breast cancer.MethodsTo evaluate the function of PinX1 in breast cancer, we used a tissue microarray (TMA) of 405 human breast cancer patients and immunohistochemistry to analyze the correlation between PinX1 expression and clinicopathologic variables and patient survival. We also detected the abilities of cell migration and invasion in breast cancer by performing cell migration and invasion assay, gelatin zymography and western blot analysis. Lastly, we set up the nude mice model by Tail vein assay to exam the functional role of PinX1 in breast cancer metastasis.ResultsWe found that low PinX1 expression was associated with lymph node metastasis (P = 0.002) and histology grade (P = 0.001) in patients, as well as with poorer overall and disease-specific survival (P = 0.010 and P = 0.003, respectively). Moreover, we identified that PinX1 inhibited the migration and invasion of breast cancer by suppressing MMP-9 expression and activity via NF-κB-dependent transcription in vitro. Finally, our mice model confirmed that PinX1 suppressed breast cancer metastasis in vivo.ConclusionsOur data revealed that low PinX1 expression was an independent negative prognostic factor for breast cancer patients. These findings suggested that PinX1 might be function as a tumor metastasis suppressor in the development and progression of breast cancer by regulating the NF-κB/MMP-9 signaling pathway, and might be a prognostic marker as well as a therapeutic target for breast cancer.

Diverse roles of C-terminal Hsp70-interacting protein (CHIP) in tumorigenesis

BackgroundThe carboxyl terminus of Hsp70-interacting protein (CHIP) is a member of E3 ubiquitin ligase, functioning as a link between the chaperone (heat shock protein 70/90) and proteasome systems, playing a vital role in maintaining the protein homeostasis in the cytoplasm. CHIP has been demonstrated to be involved in tumorigenesis, proliferation and invasion in several malignancies, regulating a number of oncogenic proteins. However, CHIP has also been implicated in the modulation of tumor suppressor proteins. The pathogenic mechanism of CHIP expression in human malignancy is not yet clear, and a number of studies have suggested that CHIP may have opposing roles in different cancers. Therefore, many studies have focused on the relationship between CHIP and carcinoma.MethodsA literature search focusing on regulation network, biological function and clinical significance of CHIP in connection with its role in cancer development was performed on the MEDLINE databases.Results and conclusionsCHIP may be a potential diagnostic biomarker and therapeutic target for human cancer, and may play different roles in different human cancers. This inconsistence might be induced by the diversity of CHIP downstream targeting proteins. Therefore, the phenotypes determined by CHIP should be dependent on the function of its specific targets in a specific type of cancer cells. Whether CHIP contributes to tumor progression or suppression in various human cancers remains unclear, suggesting the necessity of further extensive investigation of its role in tumorigenesis.

Construction of a 2D/2D g-C3N4/rGO hybrid heterojunction catalyst with outstanding charge separation ability and nitrogen photofixation performance via a surface protonation process

In this work, we report a 2D/2D hybrid heterojunction photocatalyst (PCN/rGO) with effective interfacial contact by incorporating reduced graphene oxide (rGO) and protonated g-C3N4 (PCN) synthesized via a novel electrostatic self-assembly strategy, followed by an ethylene glycol reduction process. The GCN/rGO obtained by incorporating reduced graphene oxide (rGO) and g-C3N4 without protonation (GCN) has also been prepared for comparison. PCN/rGO(0.2), with the mass ratio rGO/PCN of 0.2, exhibits the highest nitrogen photofixation performance under visible light. The NH4+ generation rate for PCN/rGO(0.2) is 42.4, 8.3 and 3.7 times higher than that of GCN, PCN and GCN/rGO(0.2). This is ascribed to the addition of rGO with PCN in a controlled ratio as well as sufficient interfacial contact by the electrostatic self-assembly process between rGO and PCN across the PCN/rGO heterojunction, for efficient charge transfer to suppress the recombination of electron–hole pairs, as evidenced by the zeta potential, XPS and PL studies. In addition, compared with GCN/rGO(0.2), the stronger interaction caused by the electrostatic attractive forces exists between PCN and rGO, leading to a better catalytic stability of PCN/rGO(0.2). This work opens up an effective way to prepare the heterojunction catalyst by incorporating two components with different surface charges.

Role of RUNX3 in Suppressing Metastasis and Angiogenesis of Human Prostate Cancer

RUNX3 (runt-related transcription factor-3) has been reported to suppress tumor tumorigenesis and metastasis in different human cancers. In this study, we used tissue microarray (TMA) to determine the significance of RUNX3 in prostate cancer progession. Our results showed ectopic expression of RUNX3 in prostate cancer tissues when compared with tumor adjacent normal prostate tissues, and reduced RUNX3 staining was significantly correlated with TNM stage. Moreover, we demonstrated that RUNX3 overexpression inhibited prostate cancer cell migration and invasion resulting from the elevated upregulation of tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), which subsequently inhibited metalloproteinase-2 (MMP-2) expression and activity in vitro. Knock down of RUNX3 expression broke up the balance of TIMP-2/MMP-2, whereas silence of TIMP-2 resulted in the inhibition of MMP-2 expression in prostate cells. We also showed that restoration of RUNX3 decreased vascular endothelial growth factor (VEGF) secretion and suppressed endothelial cell growth and tube formation. Strikingly, RUNX3 was demonstrated to inhibit tumor metastasis and angiogenesis in vivo. Altogether, our results support the tumor suppressive role of RUNX3 in human prostate cancer, and provide insights into development of targeted therapy for this disease.

Construction of g-C3N4/S-g-C3N4 metal-free isotype heterojunctions with an enhanced charge driving force and their photocatalytic performance under anoxic conditions

In heterojunction catalysts, the potential difference is the main driving force for efficient charge separation and transfer. The slight difference in the electronic band structure of the isotype heterojunction catalysts causes a poor driving force, leading to a dissatisfactory charge separation efficiency. In this work, g-C3N4/S-g-C3N4 metal-free isotype heterojunction catalysts (GCN–SCN) with an enhanced charge driving force were prepared by a two step calcination method. Anoxic photocatalytic degradation of RhB under visible light was used to evaluate the performance of the as-prepared g-C3N4 catalysts. The results indicate that this two step calcination method can markedly improve the charge driving force of the as-prepared isotype heterojunctions, leading to a more efficient charge-carrier migration. GCN–SCN displays the highest reaction rate constant of 0.0228 min−1, which is 3.5 and 2.9 times higher than that of GCN/SCN(1) and GCN/SCN(2) prepared by a one step calcination method. A linear relationship is observed between the VB driving force and RhB degradation rate. This paper provides a new perspective to prepare isotype heterojunctions with an improved charge driving force and photocatalytic performance.