RESUMO
Breast cancer poses a significant risk to women worldwide, yet specific role of SERPINA gene family in breast cancer remains unclarified. Data were collected from online databases. SERPINA family gene expression was presented, and prognosis value was evaluated. Multi-omics methods were employed to explore the SERPINA-related biological processes, followed by comprehensive analyses of their roles in breast cancer. Single-cell data were analyzed to characterize the SERPINA family gene expression in different cell clusters. We selected SERPINA5 as the target gene. Via pan-cancer analysis, SERPINA5 was also investigated in various cancers. The experimental validation was conducted in MDA-MB-231 cell line eventually. SERPINA family showed differential expression in breast cancer, which were mainly expressed in myeloid cells, epithelial cells, and dendritic cells. SERPINA5 expression was upregulated in breast cancer, which was associated with a better prognosis. Immune infiltration illustrated the positive correlativity between SERPINA5 intensity and eosinophilic recruitment. Pan-cancer analysis indicated the function of SERPINA5 as a potential biomarker in other cancers. Finally, experimental validation demonstrated that SERPINA5 contributes to lower invasion and metastatic potential of breast cancer cells. With bioinformatics analysis, the significant role SERPINA family genes functioned in breast cancer was comprehensively explored, with SERPINA5 emerging as a key gene in suppressing breast cancer progression.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/genética , Prognóstico , Transcriptoma , Células EpiteliaisRESUMO
RING finger protein 168 (RNF168) is an E3 ubiquitin ligase with the RING finger domain. It is an important protein contributing to the DNA double-strand damage repair pathway. Recent studies have found that RNF168 is significantly implicated in the occurrence and development of various cancers. Additionally, RNF168 contributes to the drug resistance of tumor cells by enhancing their DNA repair ability or regulating the degradation of target proteins. This paper summarizes and prospects the research progress of the structure and main functions of RNF168, especially its roles and the underlying mechanisms in tumorigenesis.
Assuntos
Reparo do DNA , Ubiquitina-Proteína Ligases , Humanos , Ubiquitina-Proteína Ligases/metabolismo , Carcinogênese/genética , Ubiquitinação , Dano ao DNARESUMO
Xie, T, Crump, KB, Ni, R, Meyer, CH, Hart, JM, Blemker, SS, and Feng, X. Quantitative relationships between individual lower-limb muscle volumes and jump and sprint performances of basketball players. J Strength Cond Res 34(3): 623-631, 2020-Lower body skeletal muscles play an essential role in athletic performance; however, because of the difficulty in obtaining detailed information of each individual muscle, the quantitative relationships between individual muscle volumes and performance are not well studied. The aim of this study was to accurately measure individual muscle volumes and identify the muscles with strong correlations with jump and sprint performance metrics for basketball players. Ten male varsity basketball players and 8 club players were scanned using magnetic resonance imaging (MRI) and instructed to perform various jump and sprint tests. The volumes of all lower-limb muscles were calculated from MRI and normalized by body surface area to reduce the effect of the body size differences. In analysis, feature selection was first used to identify the most relevant muscles, followed by correlation analysis to quantify the relationships between the selected muscles and each performance metric. Vastus medialis and semimembranosus were found to be the most relevant muscles for jump while adductor longus and vastus medialis were selected for sprint. Strong correlations (r = 0.664-0.909) between the selected muscles and associated performance tests were found for varsity players, and moderate correlations (r = -0.203 to 0.635) were found for club players. One possible application is that for well-trained varsity players, a targeted training scheme focusing on the selected muscles may be an effective method to further improve jump and sprint performances.
Assuntos
Desempenho Atlético/fisiologia , Basquetebol/fisiologia , Extremidade Inferior/fisiologia , Força Muscular/fisiologia , Músculo Esquelético/fisiologia , Adolescente , Humanos , Masculino , Músculo Quadríceps/fisiologia , Corrida/fisiologia , Adulto JovemRESUMO
We propose an absolute distance measurement method using alternately oscillating optoelectronic oscillators (OEOs) with high speed, high precision, and long range, and describe the dynamic characteristics of the measurement system. Measurement and reference OEOs are oscillated using a 2×2 optical switch, and rough and fine measurements are achieved by low- and high-order-mode oscillation. The distance is determined by the loop length difference between the two OEOs. OEO length control is not necessary, so the system is simple and the time per measurement is only 40â ms. The maximum measurement error is 3.4 µm with an emulated distance of 7.5â km, and the relative measurement accuracy reaches 4.5×10-10.
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There are few tumor cell subpopulations with stem cell characteristics in tumor tissue, defined as cancer stem cells (CSCs) or cancer stem-like cells (CSLCs), which can reconstruct neoplasms with malignant biological behaviors such as invasiveness via self-renewal and unlimited generation. The microenvironment that CSCs depend on consists of various cellular components and corresponding medium components. Among these factors existing at a variety of levels and forms, cytokine networks and numerous signal pathways play an important role in signaling transduction. These factors promote or maintain cancer cell stemness, and participate in cancer recurrence, metastasis, and resistance. This review aims to summarize the recent molecular data concerning the multilayered relationship between CSCs and CSC-favorable microenvironments. We also discuss the therapeutic implications of targeting this synergistic interplay, hoping to give an insight into targeting cancer cell stemness for tumor therapy and prognosis.
RESUMO
Multitarget medications represent an appealing therapy against the disease with multifactorial abnormalitiesâcancer. Therefore, simultaneously targeting son of sevenless 1 (SOS1) and epidermal growth factor receptor (EGFR), two aberrantly expressed proteins crucial for the oncogenesis and progression of prostate cancer, may achieve active antitumor effects. Here, we discovered dual SOS1/EGFR-targeting compounds via pharmacophore-based docking screening. The most prominent compound SE-9 exhibited nanomolar inhibition activity against both SOS1 and EGFR and efficiently suppressed the phosphorylation of ERK and AKT in prostate cancer cells PC-3. Cellular assays also revealed that SE-9 displayed strong antiproliferative activities through diverse mechanisms, such as induction of cell apoptosis and G1 phase cell cycle arrest, as well as reduction of angiogenesis and migration. Further in vivo findings showed that SE-9 potently inhibited tumor growth in PC-3 xenografts without obvious toxicity. Overall, SE-9 is a novel dual-targeting SOS1/EGFR inhibitor that represents a promising treatment strategy for prostate cancer.
Assuntos
Antineoplásicos , Proliferação de Células , Receptores ErbB , Neoplasias da Próstata , Proteína SOS1 , Masculino , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Humanos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Proteína SOS1/antagonistas & inibidores , Proteína SOS1/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos , Apoptose/efeitos dos fármacos , Descoberta de Drogas , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/uso terapêutico , Camundongos Nus , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB CRESUMO
Dual inhibition of tubulin and neuropilin-1 (NRP1) may become an effective method for cancer treatment by simultaneously killing tumor cells and inhibiting tumor angiogenesis. Herein, we identified dual tubulin/NRP1-targeting inhibitor TN-2, which exhibited good inhibitory activity against both tubulin polymerization (IC50 = 0.71 ± 0.03 µM) and NRP1 (IC50 = 0.85 ± 0.04 µM). Importantly, it significantly inhibited the viability of several human prostate tumor cell lines. Further mechanism studies indicated that TN-2 could inhibit tubulin polymerization and cause G2/M arrest, thereby inducing cell apoptosis. It could also suppress cell tube formation, migration, and invasion. Moreover, TN-2 showed obvious antitumor effects on the PC-3 cell-derived xenograft model with negligible side effects and good pharmacokinetic profiles. These data demonstrate that TN-2 could be a promising dual-target chemotherapeutic agent for the treatment of prostate cancer.
Assuntos
Antineoplásicos , Tubulina (Proteína) , Humanos , Linhagem Celular Tumoral , Tubulina (Proteína)/metabolismo , Neuropilina-1 , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Apoptose , Farmacóforo , Proliferação de Células , Pontos de Checagem da Fase G2 do Ciclo Celular , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/uso terapêutico , Moduladores de Tubulina/química , Polimerização , Relação Estrutura-AtividadeRESUMO
BACKGROUND AND PURPOSE: MicroRNA-9 (miR-9) has previously been described as a dual-functional RNA during breast cancer progression and its roles need to be clarified thoroughly. EXPERIMENTAL APPROACH: A miR-9 knockout mode of mouse breast cancer, the MMTV-PyMT model (PyMT-miR-9-/- ), combined with different human breast cancer cell lines were used to evaluate the effects of miR-9 on breast cancer initiation, progression and metastasis. Lin-NECs (Neoplastic mammary epithelial cells) and pNECs (Pre-neoplastic mammary epithelial cells) were isolated and subjected to tumour-initiation assay. Whole-mount staining of mammary gland and histology was performed to determine mammary gland growth. Tumour-initiating analysis combining a series of in vitro experiments were carried out to evaluate miR-9 roles in tumour-initiating ability. RNA-sequencing of human breast cancer cells, and mammary glands at hyperplastic stages and established tumours in PyMT and PyMT-miR-9-/- mice, ChIP and luciferase report assays were conducted to reveal the underlying mechanisms. KEY RESULTS: MiR-9 is ectopically expressed in breast cancer and its level is negatively correlated with the prognosis, especially in basal-like breast cancer patients. Additionally, miR-9 is essential for breast cancer progression by promoting the expansion and activity of tumour-initiating cells (TICs) in preneoplastic glands, established tumours and xenograft modes. Mechanistically, the activity of TICs hinges on a positive TGF-ß/miR-9 regulatory loop mediated by the STARD13/YAP axis. CONCLUSIONS AND IMPLICATIONS: These findings demonstrate that miR-9 is an oncogenic miRNA rather than a tumour-suppressor in breast cancer, calling for rectification of the model for this conserved and highly abundant miRNA.
Assuntos
Neoplasias da Mama , MicroRNAs , Humanos , Camundongos , Animais , Feminino , Neoplasias da Mama/metabolismo , Fator de Crescimento Transformador beta/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Transformação Celular Neoplásica/metabolismo , Células-Tronco Neoplásicas , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Proliferação de CélulasRESUMO
Homeostatic thermogenesis is an essential protective feature of endotherms. However, the specific neuronal types involved in cold-induced thermogenesis remain largely unknown. Using functional magnetic resonance imaging and in situ hybridization, we screened for cold-sensitive neurons and found preprodynorphin (PDYN)-expressing cells in the dorsal medial region of the ventromedial hypothalamus (dmVMH) to be a candidate. Subsequent in vivo calcium recording showed that cold temperature activates dmVMHPdyn neurons, whereas hot temperature suppresses them. In addition, optogenetic activation of dmVMHPdyn neurons increases the brown adipose tissue and core body temperature, heart rate, and blood pressure, whereas optogenetic inhibition shows opposite effects, supporting their role in homeostatic thermogenesis. Furthermore, we found that dmVMHPdyn neurons are linked to known thermoregulatory circuits. Importantly, dmVMHPdyn neurons also show activation during mouse social interaction, and optogenetic inhibition suppresses social interaction and associated hyperthermia. Together, our study describes dual functions of dmVMHPdyn neurons that allow coordinated regulation of body temperature and social behaviors.