Restoring BARX2 in OSCC reverses partial EMT and suppresses metastasis through miR-186-5p/miR-378a-3p-dependent SERPINE2 inhibition.

Tumor cells undergoing partial epithelial-mesenchymal transition (pEMT) are pivotal in local invasion and lymphatic metastasis of oral squamous cell carcinoma (OSCC), yet the mechanisms behind pEMT reversal remain poorly understood. In this study, the loss of BARX2 expression was revealed during the process of oral epithelial carcinogenesis and identified to activate the pEMT program, facilitate metastasis, and be associated with poor prognosis. Restoring BARX2 expression in OSCC cell lines effectively reversed tumor pEMT, evident in E/N-Cadherin switching, reduced cell invasion, proliferation, and stemness, and inhibited murine lung metastasis. BARX2 re-expression negatively correlated with several pEMT markers, notably SERPINE2, which was enriched in the invasive OSCC front, enhancing stemness and promoting metastasis, particularly in cervical lymph nodes. Furthermore, rescuing SERPINE2 impaired the inhibitory effect of BARX2 on the pEMT programs and reconstructed ECM through re-expression of MMP1. Mechanistically, we identified that BARX2 inhibited SERPINE2 through activating miR-186-5p and miR-378a-3p. These miRNAs, upregulated by BARX2, post-transcriptionally degraded SERPINE2 mRNA via targeting specific sequences. Blocking miR-186-5p and miR-378a-3p effectively abolished the negative regulatory effect of BARX2 on SERPINE2. Overall, our findings highlight BARX2 as a partial EMT-reverser in OSCC, providing fresh therapeutic prospects for restoring BARX2 signaling to inhibit invasion and metastasis.

Interaction between RAS gene and lipid metabolism in cancer.

The gene is frequently mutated and abnormally activated in many cancers，and plays an important role in cancer development. Metabolic reprogramming occurs in malignant tumors，which can be one of the key targets for anti-tumor therapy. gene can regulate lipid metabolism through AKT-mTORC1 single axis or multiple pathways，such as lipid synthesis pathways and degradation pathways. Similarly，lipid metabolism can also modify and activate RAS protein and its downstream signaling pathways. This article overviews the current research progress on the interaction between lipid metabolism and ，to provide insight in therapeutic strategies of lipid metabolism for -driven tumors.

Aberrant expression of long non-coding RNAs (lncRNAs) is involved in brain glioma development.

INTRODUCTION: Aberrant expression of long non-coding RNAs (lncRNAs) has been implicated in various diseases, including cancer. However, little is known about lncRNAs in human brain gliomas. MATERIAL AND METHODS: We examined lncRNA profiles from three glioma specimens using lncRNA expression profiling microarrays. Quantitative real-time RT-PCR was used to analyze the differential expression of raw intensities of lncRNA expression in glioma and peritumoral tissues. RESULTS: We found 4858 lncRNAs to be differentially expressed between tumor tissue and peritumoral tissue. Of these, 2845 lncRNAs were up-regulated (fold change > 3.0) and 2013 were down-regulated (fold change < 1/3). A total of 4084 messenger RNAs were also differentially expressed, including 2280 up-regulated transcripts (fold change > 3.0) and 1804 that were down-regulated (fold change < 1/3). Consistent with the microarray data, qPCR confirmed differential expression of these 6 lncRNAs (ak125809, ak098473, uc002ehu.1, bc043564, NR_027322, and uc003qmb.2) between tumor and peritumoral tissue. We next established co-expression networks of differentially expressed lncRNAs and mRNAs. Many mRNAs, such as LOC729991, NUDCD1, SHC3, PDGFA, and MDM2, and lncRNAs, such as ENST00000425922, ENST00000455568, uc002ukz.1, ENST00000502715, and NR_027873, have been shown to play important roles in glioma development. Consistent with this, pathway analysis revealed that "GLIOMA" (KEGG Pathway ID: hsa05214) was significantly enriched in tumor tissue. CONCLUSIONS: Our data suggest that altered expression of lncRNAs may be a critical determinant of tumorigenesis in glioma patients.

The function and clinical relevance of lncRNA UBE2CP3-001 in human gliomas.

INTRODUCTION: Gliomas are the most frequent primary tumors in the human brain. Recent studies have identified a class of long noncoding RNAs, named lncRNAs, which were reported to participate in regulating the development of various diseases, including gliomas. In our previous studies, we found that lncRNA UBE2CP3-001 was overexpressed in gliomas but not in normal tissue. However, the molecular functions of UBE2CP3-001 in glioma are largely unknown. MATERIAL AND METHODS: The presence of UBE2CP3-001 in U87 cells, glioma tissues and normal brain tissues was detected by real-time RT-PCR. The ability of U87 cells to migrate was analyzed using a cellular wound healing assay after downregulation of UBE2CP3-001. The survival rate of U87 cells after UBE2CP3-001 knockdown was also analyzed using the CCK8 assay. In vivo tumor weights from xenograft tumors transfected with UBE2CP3-001 shRNA were further analyzed using in vivo animal experiments. The expression levels of MMP-9 and TRAF3IP2 were determined by Western blot. RESULTS: Our data showed that UBE2CP3-001 was overexpressed in most glioma tissues (p < 0.01). Downregulation of UBE2CP3-001 could inhibit cell migration (p < 0.01) and invasiveness (p < 0.01) of U87 cells. Downregulation of UBE2CP3-001 in U87 cells also suppressed the cell proliferation (p < 0.01) and promoted apoptosis (p < 0.01). Furthermore, in vivo studies confirmed that knockdown of UBE2CP3-001 could retard the growth of U87 xenograft tumors (p < 0.01). Western blot analysis showed that knockdown of UBE2CP3-001 could effectively inhibit the expression of MMP-9 (p < 0.01) and TRAF3IP2 (p < 0.01) in U87 glioma cells. CONCLUSIONS: These data suggest an important role of UBE2CP3-001 in glioma and indicate its potential application in anti-glioma therapy.

Therapeutic effect of intensive glycemic control therapy in patients with traumatic brain injury: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Hyperglycemia is associated with dismal outcomes in patients with traumatic brain injury (TBI), which is frequently treated with insulin therapy. In this study, a systematic review and meta-analysis of the published randomized controlled trials (RCTs) was performed to assess the safety and efficacy of intensive glycemic control (IGC) versus conventional glycemic control (CGC) for patients following TBI. METHODS: Databases, including PubMed, Embase, and the Cochran database, were retrieved up to January 2018. The outcomes evaluated in this study included mortality, neurological outcome, infection rate, hypoglycemia episode, and length of stay (LOS) in intensive care unit (ICU). The enrolled trials were analyzed using the Review Manager 5.3 software. RESULTS: A total of 7 randomized controlled trials (RCTs) involving 1013 cases were enrolled in this study, and the results indicated no significant difference in 6-month mortality (risk ratio [RR], 0.92; 95% confidence interval [CI] 0.76-1.10; P = .34). Subsequently, IGC was associated with a better neurological outcome (RR, 1.22; 95% CI 1.05-1.43; P = .01), lower infection rate (RR, 0.65; 95% CI 0.51-0.82; P = .0003) and shorter LOS in ICU (mean difference [MD] = -1.37; 95%CI = -2.11, -0.63; P = .0003). In addition, IGC would also increase the risk of hypoglycemia episode (RR, 4.53; 95% CI 2.18-9.42; P < .001). CONCLUSIONS: IGC plays a protective role in improving neurological outcome, decreasing infection rate and reducing the LOS in ICU. However, IGC therapy can also remarkably increase the risk of hypoglycemia, but it will not affect the mortality in TBI patients.