LncRNA-PVT1 Inhibits Ferroptosis through Activating STAT3/GPX4 Axis to Promote Osteosarcoma Progression.

BACKGROUND: Osteosarcoma (OS) is a primary malignant bone tumor in the pediatric and adolescent populations. Long non-coding RNAs (LncRNAs), such as plasma-cytoma variant translocation 1 (PVT1), have emerged as significant regulators of OS metastasis. Recent studies have indicated that activation of signal transducer and activator of transcription 3 (STAT3) signaling, which might be controlled by PVT1, inhibits ferroptosis to promote the malignant progression of cancer. Therefore, the present study aimed to determine the role of PVT1 in OS pathogenesis and investigate whether PVT1 affects OS progression by regulating STAT3/GPX4 pathway-mediated ferroptosis. METHODS: The human OS cell line MG63 were transfected with sh-PVT1 plasmid to inhibit PVT1 expression, with or without co-transfection with a STAT3 overexpression plasmid. The expression of PVT1 was determined by real-time quantitative polymerase chain reaction (RT-qPCR). The proliferation, migration, invasion, and apoptosis of MG63 cells were determined using the cell counting kit-8 (CCK8), Transwell assay, and flow cytometry. The levels of malondialdehyde (MDA), Fe2+, and glutathione (GSH) were determined by ELISA kits, whereas reactive oxygen species (ROS) level was determined by immunofluorescence. The protein expression levels of STAT3, p-STAT3, and glutathione peroxidase 4 (GPX4) were detected by western blot (WB). RESULTS: PVT1 expression was significantly increased in MG63 cells. When knocking down PVT1 with sh-PVT1 plasmid, the proliferation, migration, and invasion of MG63 cells were markedly inhibited, while the rate of apoptosis was upregulated. Further investigation revealed that MG63 cells with PVT1 knockdown exhibited elevated levels of MDA, Fe2+, and ROS. In addition, the inhibition of PVT1 expression resulted in decreased levels of GSH and inhibited expression of p-STAT3 and GPX4. When sh-PVT1 was co-transfected with STAT3 overexpression plasmid in MG63 cells, the increased levels of MDA, Fe2+, and ROS were downregulated, and the decreased expressions of GSH, p-STAT3, and GPX4 were upregulated. CONCLUSION: PVT1 promotes OS metastasis by activating the STAT3/GPX4 pathway to inhibit ferroptosis. Targeting PVT1 might be a novel therapeutic strategy for OS treatment.

RUNX1 promotes proliferation and migration in non-small cell lung cancer cell lines via the mTOR pathway.

RUNX1, a member of the RUNX family of metazoan transcription factors, participates in the regulation of differentiation, proliferation, and other processes involved in growth and development. It also functions in the occurrence and development of tumors. However, the role and mechanism of action of RUNX1 in non-small cell lung cancer (NSCLC) are not yet clear. We used a bioinformatics approach as well as in vitro and in vivo assays to evaluate the role of RUNX1 in NSCLC as the molecular mechanisms underlying its effects. Using the TCGA, GEO, GEPIA (Gene Expression Profiling Interactive Analysis), and Kaplan-Meier databases, we screened the differentially expressed genes (DEGs) and found that RUNX1 was highly expressed in lung cancer and was associated with a poor prognosis. Immunohistochemical staining based on tissue chips from 110 samples showed that the expression of RUNX1 in lung cancer tissues was higher than that in adjacent normal tissues and was positively correlated with lymph node metastasis and TNM staging. In vitro experiments, we found that RUNX1 overexpression promoted cell proliferation and migration functions and affected downstream functional proteins by regulating the activity of the mTOR pathway, as confirmed by an analysis using the mTOR pathway inhibitor rapamycin. In addition, RUNX1 affected PD-L1 expression via the mTOR pathway. These results indicate that RUNX1 is a potential therapeutic target for NSCLC.

ZNF500 abolishes breast cancer proliferation and sensitizes chemotherapy by stabilizing P53 via competing with MDM2.

Zinc finger protein 500 (ZNF500) has an unknown expression pattern and biological function in human tissues. Our study revealed that the ZNF500 mRNA and protein levels were higher in breast cancer tissues than those in their normal counterparts. However, ZNF500 expression was negatively correlated with advanced TNM stage (p = 0.018), positive lymph node metastasis (p = 0.014), and a poor prognosis (p < 0.001). ZNF500 overexpression abolished in vivo and in vitro breast cancer cell proliferation by activating the p53-p21-E2F4 signaling axis and directly interacting with p53 via its C2H2 domain. This may prevent ubiquitination of p53 in a manner that is competitive to MDM2, thus stabilizing p53. When ZNF500-∆C2H2 was overexpressed, the suppressed proliferation of breast cancer cells was neutralized in vitro and in vivo. In human breast cancer tissues, ZNF500 expression was positively correlated with p53 (p = 0.022) and E2F4 (p = 0.004) expression. ZNF500 expression was significantly lower in patients with Miller/Payne Grade 1-2 than in those with Miller/Payne Grade 3-5 (p = 0.012). ZNF500 suppresses breast cancer cell proliferation and sensitizes cells to chemotherapy.

PHF23 promotes NSCLC proliferation, metastasis, and chemoresistance via stabilization of ACTN4 and activation of the ERK pathway.

At present, non-small cell lung cancer (NSCLC) is still one of the leading causes of cancer-related deaths. Chemotherapy remains the standard treatment for NSCLC. However, the emergence of chemoresistance is one of the major obstacles to lung cancer treatment. Plant homologous structural domain finger protein 23 (PHF23) plays crucial roles in multiple cell fates. However, the clinical significance and biological role of PHF23 in NSCLC remain elusive. The Cancer Genome Atlas data mining, NCBI/GEO data mining, and western blotting analysis were employed to characterize the expression of PHF23 in NSCLC cell lines and tissues. Statistical analysis of immunohistochemistry and the Kaplan-Meier Plotter database were used to investigate the clinical significance of PHF23. A series of in vivo and in vitro assays, including assays for colony formation, cell viability, 5-ethynyl-2'-deoxyuridine (EDU incorporation) and Transwell migration, flow cytometry, RT-PCR, gene set enrichment analysis, co-immunoprecipitation analysis, and a xenograft tumor model, were performed to demonstrate the effects of PHF23 on the chemosensitivity of NSCLC cells and to clarify the underlying molecular mechanisms. PHF23 is overexpressed in NSCLC cell lines and tissues. High PHF23 levels correlate with short survival times and a poor response to chemotherapy in NSCLC patients. PHF23 overexpression facilitates cell proliferation, migration and sensitizes NSCLC cells to Cisplatin and Docetaxel by promoting DNA damage repair. Alpha-actinin-4 (ACTN4), as a downstream regulator, interacts with PHD domain of PHF23. Moreover, PHF23 is involved in ACTN4 stabilization by inhibiting its ubiquitination level. These results show that PHF23 plays an important role in the development and progression of NSCLC and suggest that PHF23 may serve as a therapeutic target in NSCLC patients.

The Accurate Interpretation and Clinical Significance of Morphological Features of Fine Needle Aspiration Cells in Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the most common malignant neoplasm of the thyroid gland; fine needle aspiration cytology is the most basic and reliable diagnostic method before PTC operation. However, it is not clear which cell morphological changes can be used as a reliable standard for the diagnosis of PTC. A retrospective analysis was performed on 337 patients with PTC confirmed by postoperative histology. An additional 197 randomly selected patients with benign thyroid lesions were included in the study and used as a control group. True papillary arrangements, swirl arrangements, and escape arrangements had high specificity, all of which were 100%, but only swirl arrangements had ideal sensitivity (77.61%). The nuclear volume characteristics had a high sensitivity of more than 90%, but the specificities of both nuclear crowding and nuclear overlap were too low, only 16.34% and 23.35%. The sensitivities of five nuclear structural characteristics were more than 90%, but only the specificity of intranuclear cytoplasmic pseudoinclusions (INCIs) reached 100%, nuclear contour irregularity and pale nuclei with powdery chromatin also had ideal interpretation value except for grooves and marginally placed micronucleoli. Although the sensitivity of psammoma bodies (PBs) was low, the specificity was 100%. In terms of preparation methods, the method of liquid-based preparation (LBP) is obviously better than that of conventional smears. The diagnostic efficiency by the combined detection method of parallel tests showed that without reducing the specificity, the sensitivity increased with the increase of the number of morphological characteristics and finally reached 98.81%. The INCIs and swirl arrangements are the most common and important indicators for the diagnosis of PTC, whereas papillary-like arrangements, the crowding and overlap of nuclear, grooves, marginally placed micronucleoli, and multinucleated giant cells are of little significance for the diagnosis of PTC.

NtNCED3 regulates responses to phosphate deficiency and drought stress in Nicotiana tabacum.

Plants are sessile and encounter to abiotic environmental stressors, such as nutrient deficiency and drought stress. Identifying stress tolerance genes and their mechanisms is vital to ensuring plant survival. In this study, we characterized NCED3 in the tobacco plant Nicotiana tabacum, a key enzyme in the biosynthesis of abscisic acid that is widely involved in abiotic stress responses, using overexpression and RNA interference knockdown. Overexpression of NtNCED3 promoted primary root development, leading to increased dry weight, root-to-shoot ratio, photosynthetic capacity, and acid phosphatase activity, coinciding with highly increased phosphate uptake capability under low phosphate conditions. Under both drought and extreme phosphate deficiency conditions, the phosphate starvation response preceded the drought stress response. However, under high phosphate conditions, the drought stress phenotype emerged before the symptoms of phosphate deficiency. Plants overexpressing NtNCED3 grew better than the wild-type and NtNCED3 knockdown plants, with more developed root systems and higher biomass, phosphorus content, and hormone content. This study provides evidence that NtNCED3 enzyme participates in plant responses to phosphate deficiency and drought stress in N. tabacum, and NtNCED3 may serve as a potentially valuable gene for genetic modification of plant tolerance to both drought stress and phosphate starvation.

Autophagy inhibition and reactive oxygen species elimination by acetyl-CoA acetyltransferase 1 through fused in sarcoma protein to promote prostate cancer.

BACKGROUND: Prostate cancer is a major health issue affecting the male population worldwide, and its etiology remains relatively unknown. As presented on the Gene Expression Profiling Interactive Analysis database, acetyl-CoA acetyltransferase 1 (ACAT1) acts as a prostate cancer-promoting factor. ACAT1 expression in prostate cancer tissues is considerably higher than that in normal tissues, leading to a poor prognosis in patients with prostate cancer. Here, we aimed to study the role of the ACAT1-fused in sarcoma (FUS) complex in prostate cancer and identify new targets for the diagnosis and treatment of the disease. METHODS: We conducted immunohistochemical analysis of 57 clinical samples and in vitro and in vivo experiments using a mouse model and plasmid constructs to determine the expression of ACAT1 in prostate cancer. RESULTS: The relationship between the expression of ACAT1 and the Gleason score was significant. The expression of ACAT1 was higher in tissues with a Gleason score of > 7 than in tissues with a Gleason score of ≤7 (P = 0.0011). In addition, we revealed that ACAT1 can interact with the FUS protein. CONCLUSIONS: In prostate cancer, ACAT1 promotes the expression of P62 and Nrf2 through FUS and affects reactive oxygen species scavenging. These effects are due to the inhibition of autophagy by ACAT1. That is, ACAT1 promotes prostate cancer by inhibiting autophagy and eliminating active oxygen species. The expression of ACAT1 is related to prostate cancer. Studying the underlying mechanism may provide a new perspective on the treatment of prostate cancer.

Clear cell sarcoma of soft tissue with plasmacytoid morphology: A rare case report.

RATIONALE: Clear cell sarcoma of soft tissue (CCSST) is a rare malignant tumor that occurs in the extremities of young adults. CCSST has been documented to have atypical histopathological features, such as epidermotropism or myxoid differentiation, which may set pitfalls in the differential diagnosis. We report a case of CCSST with plasmacytoid morphology which has never been described. PATIENT CONCERNS: A 15-year-old male, presented with a 5-cm mass in his left inguinal area. DIAGNOSIS: Positron emission tomography-computed tomography examination showed nodules in the left groin and the lung, the latter was considered metastasis. A core needle biopsy with the diagnosis of CCSST with plasmacytoid morphology was made according to histology, immunostaining, and molecular analysis. INTERVENTIONS: The patient received chemotherapy of doxorubicin and ifosfamide. OUTCOMES: The patient failed to respond to the standard chemotherapy and deceased twelve months after diagnosis. LESSONS: This special case of CCSST with plasmacytoid features demonstrated a morphological variation never been documented and may easily lead to misdiagnosis. For such cases, molecular analysis is essential to provide solid evidence for accurate diagnosis.

Case report: Intraoperative frozen section analysis of Thyroid paraganglioma.

Paraganglioma (PGL) is a neuroendocrine tumor that arises from the sympathetic or parasympathetic paraganglia. Primary thyroid PGL is extremely rare. PGL may be difficult to diagnose on frozen sections because its histopathological features, such as polygonal tumor cells with eosinophilic cytoplasm arranged irregularly, overlap with those of thyroid follicular adenoma. We present a case of thyroid PGL in a female patient and provide a detailed description of the patient's clinicopathologic characteristics. Cervical computed tomography showed a left thyroid mass with uneven density. Intraoperative frozen section analysis showed an uneven fibrous septa and rich networks of delicate vessels surrounding tumor cell nests. The tumor cells were polygonal or epithelioid with eosinophilic cytoplasm, arranged in a nest, trabecular, or organoid pattern were and diagnosed as thyroid follicular adenoma. However, in postoperative immunohistochemistry, these were diagnosed as thyroid PGL. The postoperative recovery was uneventful. The patient showed no signs of tumor recurrence or metastasis until 16 months of follow-up. Herein, we summarize the characteristic features of thyroid PGL based on frozen section analysis. In the appropriate clinical context, its proper use as diagnostic and differential diagnostic management strategies is recommended.

HSF1 is a driver of leukemia stem cell self-renewal in acute myeloid leukemia.

Acute myeloid leukemia (AML) is maintained by self-renewing leukemic stem cells (LSCs). A fundamental problem in treating AML is that conventional therapy fails to eliminate LSCs, which can reinitiate leukemia. Heat shock transcription factor 1 (HSF1), a central regulator of the stress response, has emerged as an important target in cancer therapy. Using genetic Hsf1 deletion and a direct HSF1 small molecule inhibitor, we show that HSF1 is specifically required for the maintenance of AML, while sparing steady-state and stressed hematopoiesis. Mechanistically, deletion of Hsf1 dysregulates multifaceted genes involved in LSC stemness and suppresses mitochondrial oxidative phosphorylation through downregulation of succinate dehydrogenase C (SDHC), a direct HSF1 target. Forced expression of SDHC largely restores the Hsf1 ablation-induced AML developmental defect. Importantly, the growth and engraftment of human AML cells are suppressed by HSF1 inhibition. Our data provide a rationale for developing efficacious small molecules to specifically target HSF1 in AML.

A detection panel of novel methylated DNA markers for malignant pleural effusion.

Background: Cytology remains the gold standard for the detection of malignant cells in pleural effusion. However, its sensitivity is limited. The aim of this study was to establish a novel panel of cancer-specific methylated genes for the differential diagnosis of malignant pleural effusion (MPE). Methods: A cohort of 100 cancer patients (68 lung cancer, 32 other malignant tumors) and 48 patients with benign disease presenting with pleural effusion was prospectively enrolled. Pleural effusion was evaluated by means of cytopathological investigation and DNA methylation of SHOX2, RASSF1A, SEPTIN9 and HOXA9 in the cellular fraction. DNA methylation in bisulfite-converted DNA was determined using quantitative methylation-specific real-time PCR (MS-PCR). Cytopathological and DNA methylation results were evaluated with regard to the final clinical diagnosis. Results: The LungMe® SHOX2 and RASSF1A Assay (Tellgen Corporation, China) has been reported to be highly sensitive and specific for lung cancer using bronchial aspirates. As expected, LungMe® detected metastases of lung cancer (sensitivity: 76.5%) as well as metastases of other malignant tumors (sensitivity: 68.8%). OncoMe, a novel combination of SHOX2, RASSF1A, SEPTIN9 and HOXA9 methylation, led to an additional 11% increase in the detection rate of MPE, resulting in a sensitivity of 85% and a specificity of 96%. Overall, OncoMe showed a higher positive detection rate in SCLC (100%), LUAC (87%), OC (100%), BC (92.9%), GC (80.0%), and MESO (80%) than in LUSC (50%). Cytopathological analyses only detected 23 positive samples, which were all positively measured by both LungMe® and OncoMe. Conclusion: OncoMe has potential for use as a biomarker for the detection of MPE, even not limited to lung cancer.

P130cas-FAK interaction is essential for YAP-mediated radioresistance of non-small cell lung cancer.

Based on the RNA-sequencing data, previous studies revealed that extracellular matrix receptor interaction and focal adhesion signaling pathways were enriched in radioresistant non-small cell lung cancer (NSCLC) cell lines. As the principal members of these signaling pathways, recent studies showed that FAK controlled YAP's nuclear translocation and activation in response to mechanical activation. However, the underlying mechanisms are largely unknown. This study was designed to determine whether P130cas plays a role in FAK-YAP axis-mediated radioresistance. We found that P130cas promoted proliferation, altered the cell cycle profile, and enhanced tumor growth using cell lines and xenograft mouse models. After treating the cell lines and xenograft models with a single dose of 5 Gy irradiation, we observed that P130cas effectively induced radioresistance in vitro and in vivo. We confirmed that P130cas interacted with and promoted YAP stabilization, thereby facilitating YAP's activation and nuclear translocation and downregulating the radiosensitivity of NSCLC. Our data also revealed that P130cas and FAK directly interacted with each other and worked together to regulate YAP's activation and nuclear translocation. Furthermore, the present study identified that P130cas, FAK and YAP formed a triple complex to induce radioresistance. Using P130cas-ΔSH3, FAK- P712/715A mutant, YAP-ΔSH3bm and YAP-ΔWW mutant, our results showed that targeting P130cas-FAK interaction may be a more cost-effective way to overcome the YAP activation mediated radioresistance in NSCLC. Using the data of the public database and our clinical samples, the present study suggested that the expression of P130cas correlated with YAP expression and indicated a poor overall response rate of NSCLC patients who underwent radiation therapy. Overall, our study extends the knowledge of FAK-YAP interaction and provides new insight into understanding the underlying mechanisms to overcome the radioresistance of NSCLC.

ARHGEF40 promotes non-small cell lung cancer proliferation and invasion via the AKT-Wnt axis by binding to RhoA.

Rho guanine nucleotide exchange factor 40 (ARHGEF40) is a member of the Dbl-family of guanine nucleotide factor proteins. However, its expression pattern and biological function in malignant tumors, notably in nonsmall cell lung cancer (NSCLC) are currently unknown. The present study demonstrated that ARHGEF40 was highly expressed in NSCLC specimens and that its expression was significantly associated with advanced TNM stage (p < 0.001), lymph node metastasis (p = 0.002), and poor prognosis (p = 0.0056). In addition, ARHGEF40 accelerated nuclear translocation of the key component ß-catenin and increased the expression levels of the Wnt signaling pathway targets c-myc, cyclin D1 and MMP7. Moreover, it promoted lung cancer cell proliferation and invasion in vitro and in vivo. To elucidate the underlying molecular mechanism, the current study demonstrated that ARHGEF40 could induce activation of the Wnt signaling pathway by increasing the phosphorylation levels of AKT and GSK3ß via interaction with RhoA. Moreover, the Dbl homology (DH)-pleckstrin homology (PH) domain of ARHGEF40 was responsible for this interaction. Its deletion abolished the binding, which blocked the activation of the Wnt signaling. Taken together, the data indicated that ARHGEF40 promoted the malignant phenotype of lung cancer cells by activating the AKT-Wnt axis. This was achieved by its interaction with RhoA via the DH-PH domain. ARHGEF40 may serve as a novel target for NSCLC treatment.

Rab22a Promotes Epithelial-Mesenchymal Transition in Papillary Thyroid Carcinoma by Activating PI3K/AKT/mTOR Signaling Pathway.

Background: Rab22a is a member of the RAS superfamily, involved in early endosome formation and intracellular vesicle transport. Rab22a is significantly upregulated in a variety of malignant tumors. However, its function in thyroid cancer has never been addressed. Methods: The expression of Rab22a in paraffin sections of 101 patients was detected by immunohistochemical staining. By upregulating and downregulating the expression of Rab22a in thyroid cancer cell lines, the effect of Rab22a on cell proliferation, invasion, and migration was analyzed. Co-IP was employed, and the interaction between Rab22a and PI3Kp85α was shown. The function of Rab22a on PI3K/AKT/mTOR signaling and epithelial-mesenchymal transition (EMT) was further studied by western blot analysis. Results: Immunostaining showed that Rab22a was significantly overexpressed in thyroid cancer tissues but negative in adjacent normal tissues or nodular goiters. The proliferation, migration, invasion, and EMT in papillary thyroid carcinoma cell lines were enhanced upon Rab22a overexpression but inhibited after knocking down Rab22a. The co-IP assay demonstrated an interaction between Rab22a and PI3K85α, an effector of PI3K. We further found that Rab22a can activate the PI3K/AKT/mTOR signaling pathway. However, the ability of Rab22a to promote the proliferation, invasion, migration, and EMT of papillary thyroid carcinoma cells was significantly inhibited after being treated with LY294002, a PI3K inhibitor. Conclusions: Rab22a can promote the EMT process and enhance proliferation, migration, and invasion of papillary thyroid carcinoma cells by activating the PI3K/AKT/mTOR signaling pathway. Our study provides new pathological diagnosis clues and clinical treatment targets for thyroid cancer.

Diffuse midline glioma with H3-K27M mutation: A rare case with GFAP-positive anucleate whorled patterns.

INTRODUCTION: Diffuse midline glioma with H3-K27M mutation is an infiltrative high-grade glioma, with predominantly astrocytic differentiation. PATIENT CONCERNS: A 54-year-old Chinese woman presented with memory loss for a month and walking instability for 15 days. DIAGNOSIS: Magnetic resonance imaging showed a mass shadow of isometric T1 and slightly longer T2 with mild mixed signals in the third ventricle of the suprasellar region. Histologically, the tumor was primarily sheet-like, with many "anucleate areas" composed of long and thin fibrillary processes of the bipolar cells, which formed "whorls." The neoplastic nuclei were ovoid and moderate in size. The tumor showed brisk mitotic activity and vascular proliferation, with no necrosis. In addition to histone H3K27M mutation, immunohistochemical staining showed that the tumor cells were positive for glial fibrillary acidic protein, oligodendrocyte transcription factor 2, alpha-thalassemia/mental retardation syndrome X, S-100 and Vimentin. The "anucleate areas" were positive for glial fibrillary acidic protein and negative for synaptophysin. The Ki-67 proliferation index was about 10%. Molecular genetic analyses detected H3F3A K27M mutation, but no mutations in IDH1 or IDH2, TERT promoter mutations, MGMT promoter methylation, KIAA1549-BRAF fusion or deletion of 1p/19q were found. Based on these findings, the patient was diagnosed as diffuse midline glioma with H3-K27M mutation in the third ventricle, corresponding to WHO grade 4. INTERVENTIONS: A craniotomy with total excision of the tumor was performed. OUTCOMES: After surgery, she was routinely treated with temozolomide for chemotherapy and synchronous radiotherapy. It has been 11 months now, and the patient is living well. CONCLUSION: This case report provides information on the microscopic morphological features of diffuse midline glioma with H3K27M mutation, which can help pathologists to make a definitive diagnosis of this tumor.

KBTBD7 promotes non-small cell lung carcinoma progression by enhancing ubiquitin-dependent degradation of PTEN.

The Kelch repeat and BTB domain containing 7 (KBTBD7) was first cloned in 2010. Its function as a transcriptional activator and a substrate adaptor during the ubiquitination process was soon found. KBTBD7 was shown to be involved in excessive inflammation after myocardial infarction, brain development, and neurofibromin stability. However, studies on the role of KBTBD7 in solid tumors, especially lung cancer, are still lacking. Therefore, in this study, we investigate the role of KBTBD7 in non-small cell lung cancer (NSCLC). Immunohistochemical staining of 104 paired NSCLC and peritumoral normal specimens indicated that KBTBD7 was highly expressed in NSCLC tissues and positively correlated with the histological type, P-TNM stage, lymph node metastasis, and tumor size. KBTBD7 was also well-expressed in NSCLC cell lines, and downregulation of KBTBD7 resulted in inhibition of NSCLC cell proliferation and invasion. Further investigation showed that KBTBD7 enhanced ubiquitin-dependent degradation of PTEN, thus activating EGFR/PI3K/AKT signaling and promoting NSCLC cell proliferation and invasion by regulating CCNE1, CDK4, P27, ZEB-1, Claudin-1, ROCK1, MMP-9, and E-cadherin protein levels. Our results indicate that KBTBD7 may be a potential therapeutic target for the treatment of NSCLC.

Rab22a promotes the proliferation, migration, and invasion of lung adenocarcinoma via up-regulating PI3K/Akt/mTOR signaling pathway.

Rab22a, a member of the proto-oncogene RAS family, belongs to the Rab5 subfamily. It participates in early endosome formation and regulates vesicle trafficking. The relationship between Rab22a and tumorigenesis remains elusive. In non-small cell lung cancer specimens, immunohistochemical staining showed consistently high expression of Rab22a in lung adenocarcinoma, but not in squamous cell carcinoma. In lung adenocarcinoma cell lines, A549 and H1299, transfection with Rab22a significantly promoted cell proliferation, migration, and invasion, whereas interference with Rab22a specific siRNA significantly inhibited the above capacities. Transfection with Rab22a also up-regulated the phosphorylation levels of core effector proteins on the PI3K/Akt/mTOR pathway. The Co-IP assay further confirmed the interaction between Rab22a and PI3Kp85α, the core regulatory subunit of PI3K. Application of rapamycin, the mTOR inhibitor, significantly reduced the upregulation of the proliferation, migration, and invasion abilities of lung adenocarcinoma cells transfected with Rab22a. These results suggest that Rab22a can promote the malignant phenotype of lung adenocarcinoma by upregulating the PI3K/Akt/mTOR signaling pathway, and may function as a potential anti-tumor therapeutic target.

LncRNA SLC16A1-AS1 regulates the miR-182/PDCD4 axis and inhibits the triple-negative breast cancer cell cycle.

PURPOSE: Although SLC16A1-AS1 is involved in lung cancer, its function in breast cancer is still elusive. We observed downregulation of SLC16A1-AS1 expression in triple-negative breast cancer (TNBC) by analyzing TCGA dataset. Therefore, we analyzed the function of SLC16A1-AS1 in TNBC. METHODS: We observed downregulation of SLC16A1-AS1 expression in TNBC by analyzing TCGA dataset. Therefore, we analyzed the function of SLC16A1-AS1 in TNBC. RESULTS: SLC16A1-AS1 expression was downregulated in TNBC tissues. SLC16A1-AS1 interacted with miR-182, whereas SLC16A1-AS1 and miR-182 overexpression failed to affect their expression. SLC16A1-AS1 overexpression upregulated the expression of PDCD4, a downstream target of miR-182. SLC16A1-AS1 and PDCD4 overexpression suppressed cell cycle progression from the G1 phase to the G2 phase. MiR-182 and silencing of PDCD4 played the opposite role. Additionally, miR-182 overexpression inhibited the role of SLC16A1-AS1 overexpression on cell cycle progression in both BT-549 and BT20 cells. The cell proliferation assay showed that SLC16A1-AS1 and PDCD4 overexpression decreased the cell proliferation rate. CONCLUSION: SLC16A1-AS1 may inhibit cell cycle progression and restrain TNBC cell proliferation by regulating the miR-182/PDCD4 axis.

Crosstalk between peripheral and the brain-resident immune components in epilepsy.

Epilepsy is one of the most common neurology diseases. It is characterized by recurrent, spontaneous seizures and accompanied by various comorbidities which can significantly affect a person's life. Accumulating evidence indicates an essential pathophysiological role for neuroinflammation in epilepsy, which involves activation of microglia and astrocytes, recruitment of peripheral leukocytes into the central nervous system, and release of some inflammatory mediators, including pro-inflammatory factors and anti-inflammatory cytokines. There is complex crosstalk between the central nervous system and peripheral immune responses associated with the progression of epilepsy. This review provides an update of current knowledge about the contribution of this crosstalk associated with epilepsy. Additionally, how gut microbiota is involved in epilepsy and its possible influence on crosstalk is also discussed. Such recent advances in understanding suggest innovative methods for targeting the molecules correlated with the crosstalk and may provide a better prognosis for patients diagnosed with epilepsy.

Systematic analysis of the non-specific lipid transfer protein gene family in Nicotiana tabacum reveal its potential roles in stress responses.

Plant non-specific lipid transfer proteins (nsLTPs) are characterized by an eight-cysteine motif backbone stabilized by four disulfide bonds; these proteins can bind or transfer lipids. NsLTPs play important roles in plant growth and development, and in the responses to abiotic and biotic stresses. In this study, 50, 51, and 100 nsLTPs from Nicotiana sylvestris, N. tomentosiformis, and their descendant N. tabacum, respectively, were identified and classified into six types (I, II, IV, V, VII, and VIII). The phylogeny, gene structures, motifs, tertiary structures, gene duplications and expression patterns were systematically analyzed. The intron/exon patterns and the conserved motifs were highly similar among the same types of nsLTP genes. Purifying selection and segmental duplication dominated the expansion of the nsLTPs family during evolution. Cis-regulatory elements of the NtLTP promoters were involved in light responsiveness, abiotic stress, and phytohormone responsiveness. Expression pattern analysis using RNA-seq and qPCR revealed that NtLTP family genes exhibited tissue-specific expression patterns and they have potential roles in response to abiotic and biotic stresses, especially drought stress, and resistance to black shank and bacterial wilt. Furthermore, overexpression of NtLTPI.38 in tobacco increased drought tolerance by improving the antioxidant defense ability, through reducing O2•- and H2O2 accumulation and increasing the number of lateral roots. These results provide a comprehensive overview of this gene family and provide valuable insights for the functional characterization of nsLTP family genes.