JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

Colorectal carcinoma (CRC) poses a serious risk to global human health. Long non-coding RNAs (LncRNAs) play an important role in the pathogenesis of CRC. There is a scarcity of data about a newly identified lncRNA, FAM30A. Our major objective is to investigate the role of FAM30A in the process of CRC. Gene expression data and correlated clinical information were retrieved and downloaded from public databases to identify differentially expressed genes linked to CRC. The expression of FAM30A was identified in clinical samples and CRC cell lines using via Quantitative Real-time Polymerase Chain Reaction (qPCR) assay also. The survival significance of FAM30A was determined via R package “survival.” Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to identify FAM30A-related signalling pathway. The levels of proteins expression were determined by western blot assay. The effect of FAM30A on CRC cell biological behaviours was evaluated by cell function experiments. FAM30A was identified down-regulated in CRC based on the data from public database. FAM30A had lower expression in CRC clinical samples and cell lines. Low FAM30A expression was positively related to a poor prognosis in CRC patients. After FAM30A was overexpressed, the proliferation, invasion, and migration abilities of CRC cells were decreased, and the rate of CRC cell apoptosis increased. Furthermore, overexpression of FAM30A could block JAK–STAT signalling. FAM30A suppresses proliferative, invasive, and migratory abilities of CRC through blocking JAK–STAT signalling. Thus, it can be a novel biomarker of CRC prognosis.

Gliomas, the most prevalent primary malignancy of the central nervous system, is characterised by its high mortality rates and unfavourable prognosis. Despite extensive research, the underlying mechanisms of glioma pathogenesis remain elusive. The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases provided the lower-grade gliomas (LGG) transcriptome and related clinical data, which were downloaded separately. It was determined what the clinical data differences were between the two groups based on the median reticulon-4 (RTN4) expression group. The R language's survminer tool was utilised to examine the variations in survival between the RTN4 high and low-expression groups. The GeneMANIA database was searched for genes that might interact with RTN4, and these genes were then used to create extensive coexpression networks. Cox regression analysis, both univariate and multivariate, was used to filter out the independent prognostic factors influencing tumour growth. Based on independent prognostic parameters, a nomogram was created to predict prognosis. The model was assessed both internally and externally using receiver operating characteristic curve (ROC) and correcting curves. The R cibersort package was utilised to assess the level of immune infiltration abundance. We further validated our findings with clinical tissues using immunohistochemistry approaches. Statistical significance was determined using the Wilcoxon signed-rank test, with a p value of < 0.05 considered significant. RTN4 expression in the tumour group was higher than in the normal group (p < 0.001), and a high-expression level was linked to a poor prognosis (p = 0.028). Patients with elevated RTN4 expression exhibited significant differences from normal brain tissue samples when stratified analysis of LGG patients by sex or radiation treatment was performed (p < 0.001). The immune cell infiltration data demonstrated that the two groups' expressions of various immune cells differed, with pDC cells showing the greatest correlation (−0.421). Univariate and multivariate Cox regression study showed that RTN4, isocitrate dehydrogenase (IDH) mutation, 1p19q codeletion and nia age could be employed as independent prognostic factors for LGG, and the correction curve of the model fit well. Ultimately, clinical samples' immunohistochemistry revealed that RTN4 was markedly overexpressed in low-grade gliomas. High RTN4 expression was strongly associated with a poor prognosis in LGG patients. RTN4 may serve as a prognostic biomarker for patients with LGG and represents a potential therapeutic target for immunotherapy in this patient population.

Tetralogy of Fallot (TOF) is a common congenital heart disease. In this study, we proposed that cAMP response element-binding protein (CREB)-binding protein (CBP) regulates the proliferation and apoptosis in TOF by interacting with the sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA). To confirm this, we collected right ventricle tissue samples from TOF patients during surgery to correct the deformity and from the donors. We performed IHC, IF, RT-qPCR, WB and ChIP experiments. The analysis of these experiments shows that the expression of CBP is higher in TOF patients than in healthy individuals. Further, the RT-qPCR results indicated that the CBP and SERCA mRNA in TOF patients were significantly higher than in the healthy donors. Similarly, WB results suggested that the expression of CBP and SERCA was predominantly elevated in TOF patients compared to healthy individuals. Further, the AC16 cell line with CBP knockdown reveals high expression of the Edu compared to normal cells, and the percentage of the cell cycle in the M phase was elevated in the CBPi group. In addition, the CCK-8 cell viability assay showed more proliferation in the CBPi group than in the control group at different time points. Moreover, the RT-qPCR results indicated a lower expression of SERCA after the knockdown of CBP and CREB. Finally, the ChIP assay shows that CREB binds to the promoter of SERCA, and the CBP enrichment decreased after the CREB knockdown. In conclusion, these results suggest that CBP interacts with SERCA to regulate cell proliferation and apoptosis during heart development and that up-regulation of CBP leads to TOF.

The family of protein arginine methyltransferases (PRMTs) occupies an important position in biology, especially during the initiation and development of cancer. PRMT3 and CARM1(also known as PRMT4), being type I protein arginine methyltransferases, are key in controlling tumour progression by catalysing the mono-methylation and asymmetric di-methylation of both histone and non-histone substrates. This paper reviews the functions and potential therapeutic target value of PRMT3 and CARM1 in a variety of cancers. Studies have identified abnormal expressions of PRMT3 and CARM1 in several malignancies, closely linked to cancer progression, advancement, and resistance to treatment. Such as hepatocellular carcinoma, colorectal cancer, ovarian cancer, and endometrial cancer. These findings offer new strategies and directions for cancer treatment, especially in enhancing the effectiveness of conventional treatment methods.

Gliomas are the most ordinary primary virulent brain tumours and commonly used clinical treatments include tumour resection, radiation therapy and chemotherapy. Although significant progress has been made in recent years in progression-free survival (PFS) and overall survival (OS) for patients with high-grade gliomas, the prognosis for patients remains poor. Chemoresistance refers to the phenomenon of decreased sensitivity of tumour cells to drugs, resulting in reduced or ineffective drug efficacy, and is an important cause of failure of tumour chemotherapy. Exosomes, a type of extracellular vesicle, are secreted by cancer cells and various stromal cells in the tumour microenvironment (TME) and transfer their inclusions to cancer cells, increasing chemoresistance. Furthermore, depletion of exosomes reverses certain detrimental effects on tumour metabolism and restores sensitivity to chemotherapeutic agents. Here, we summarised the correlation between exosomes and resistance to chemotherapeutic agents in glioma patients, the mechanisms of action of exosomes involved in resistance and their clinical value. We aimed to afford new thoughts for research, clinical diagnosis and intervention in the mechanisms of chemoresistance in glioma patients.

Oral squamous cell carcinomas (OSCCs), like several solid tumours, contain heterogeneous subpopulations of a small subset of cancer cells, termed cancer stem cells (CSCs), that are highly relevant to cancer metastasis and invasive properties. CSCs have also shown a high capacity to survive against various stressful environments, such as hypoxia. However, the molecular underpinnings behind the high potential of CSCs to survive under this stress remain unclear. The current study aimed to investigate the significance of autophagy systems in oral CSC maintenance and survival under stress conditions. Human OSCC cell lines OECM-1 and OECM-1 CSCs were cultured in different hypoxic time periods for proliferation and cytotoxicity analyses. The stemness property of CSCs is evaluated by sphere formation, transwell and wound healing assays protein expression of stemness, and epithelial-to-mesenchymal transition markers. Mitochondrial functions, including mitochondrial ROS generation, mitochondria dynamics, mitophagy, and mitochondrial metabolism (glycolysis and oxidative phosphorylation [OXPHOS]) were examined by western blotting, immunohistochemistry, and XF-seahorse assays, respectively. Under hypoxia, oral CSCs showed a higher proliferation rate with increased invasion/migration/EMT properties than OECM-1 cells. Further, hypoxia-induced BNIP3-driven mitophagy was activated in OECM-1 CSCs than in OECM-1 cells, which also triggered a metabolic shift towards OXPHOS, and BNIP3/-L silencing by siRNA significantly attenuated OECM-1 CSCs stemness features. TCGA data analyses also revealed a higher BNIP3 expression in head and neck squamous carcinoma patients' tumour samples associated with lower patient survival. Collectively, our results revealed a BNIP3/-L-driven autophagy contributes to the OECM-1 CSCs stemness features under hypoxia, suggesting a novel therapeutic strategy involving BNIP3 and autophagy inhibition in oral CSCs.

Osteosarcoma, the most common primary bone cancer in adolescents, often carries a grim prognosis due to its high metastatic potential. Due to its low bioavailability, curcumin limits its adjuvant efficacy in improving prognosis and long-term survival in osteosarcoma patients. To investigate apoptosis induced by the synthesised curcumin analog GO-Y030 in human osteosarcoma cells, flow cytometry, annexin V-fluorescein isothiocyanate-labelled/propidium iodide staining, human apoptosis array, and Western blotting were used. GO-Y030 dose-dependently reduced viability and induced sub-G1 arrest and apoptosis in human osteosarcoma U2OS and 143B cells. GO-Y030 significantly activated caspases 8, 9, and 3, while suppressing cellular inhibitors of apoptosis protein 1 (cIAP-1) and X-chromosome-linked IAP. GO-Y030 increased the phosphorylation of extracellular signal-regulated protein kinases (ERK)1/2, c-Jun N-terminal kinases (JNK)1/2, and p38. Inhibitors of JNK (JNK-IN-8) and p38 (SB203580) suppressed GO-Y030-induced cleavage of caspases 8, 9, and 3, whereas co-treatment with the ERK inhibitor (U0126) did not lessen their activation. Overall, GO-Y030 triggers both extrinsic and intrinsic apoptotic cascades in U2OS and 143B cells by activating the JNK1/2 and p38 pathways, shedding light on its mechanism of action against human osteosarcoma cells.

This study investigated the effect of 8 weeks of high-intensity interval training (HIIT) on oxidative stress, inflammation, and apoptosis in rats with type 2 diabetes (T2D), focusing on the role of the Humanin (HN). In this study, 28 male Wistar rats were assigned to one of four groups: healthy control (CO), diabetes control (T2D), exercise (EX), and diabetes + exercise (T2D + EX). After diabetes induction (2-month high-fat diet and injection of 35 mg/kg streptozotocin), the animals in the EX and T2D + EX groups underwent an 8-week HIIT protocol (4–10, interval of 80%–100% of maximum speed). HOMA-IR, fasting blood glucose, and HN levels were measured in the serum. The expression of HN, Bax, Bcl-2, CAT, GPx, MDA, TNFα, and IL-10 was measured in the soleus muscle. Our results showed that the serum level of HN and the muscle levels of IL-10, SOD, CAT, and Bax were higher in the T2D + EX group than in the T2D group. However, the HOMA-IR index and the muscle levels of MDA, TNFα, and Bcl-2 were lower in the T2D + EX group than in the T2D group. Muscle levels of HN and GPx showed no significant difference between the T2D + EX and T2D groups. The result of Pearson analysis showed a significant correlation between HN and MDA, SOD, Bax and Bcl-2. This study provides evidence that there is a correlation between serum Humanin levels and HIIT. HIIT benefits T2D rats by reducing inflammation and oxidative stress. Given Humanin's established involvement in inflammation and oxidative stress, it is possible that the benefits of HIIT on T2D rats are mediated by humanin.

DNA methylation is a crucial epigenetic alteration involved in diverse biological processes and diseases. Hippo signalling pathway is a key signalling regulatory network in the growth and development of tissues and organs. Nevertheless, the precise role of DNA methylation and Hippo signalling pathway during liver regeneration (PH) is still unclear. In this study, we investigated the regulatory mechanism of LATS1, a pivotal protein in the Hippo signalling pathway, on liver regeneration and explored the specific mechanism of DNA methylation regulating LATS1. To analyse the regulation of LATS1 by DNA methylation, following 2/3 partial hepatectomy (PH) in liver-specific AAV-8 shDNMT3B deleted mice (DNMT3B, KD) mice and sex-matched AAV-8 shControl (Control). We determined that DNMT3B regulates the protein expression of LATS1 by DNA methylation. miR-29b-3p significantly regulates the expression of DNMT3B and alters LATS1 expression to inactivate the Hippo signalling pathway, thereby reducing the expression of cell proliferation and cycle proteins and inhibiting liver regeneration. Our results indicated that the miR-29b-3p/DNMT3B regulatory axis influences LATS1 expression through DNA methylation, and thereby promotes liver regeneration.

Zhou J, Fan Y, Zhong J, et al. TAK1 mediates excessive autophagy via p38 and ERK in cisplatin-induced acute kidney injury. Journal of cellular and molecular medicine 2018;22(5):2908–2921. doi:10.1111/jcmm.13585.

In Zhou Jun et al., the immunohistochemistry (IHC) image for sham in Figure 1H was inadvertently misused during the figure preparation process. This correction does not affect the figure legends or the conclusions drawn in the study. The correct figures are shown below.