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BMC Cancer ; 21(1): 760, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193109


BACKGROUND: Breast cancer is the leading cause of cancer-related deaths in females worldwide. Formin-like protein 2 (FMNL2) is a member of formin family that governs cytokinesis, cell polarity, morphogenesis and cell division. To our knowledge, the function of FMNL2 in breast cancer proliferation still remains uncovered. METHODS: Tumor immune estimation resource (TIMER) analysis was used to detect the correlation between FMNL2 and Ki67 in breast cancer tissues. Quantitative real-time transcription polymerase chain reaction (qRT-PCR) and western blotting were performed to analyze the expression in human breast cancer cells. Moreover, RNA interference (RNAi) and plasmids were performed to silence and overexpress FMNL2 and p27. The CCK8, MTT, cell counting, colony formation, and 5-ethynyl-2-deoxyuridine (EdU) incorporation assays were used to detect cell proliferation, respectively. Flow cytometry analysis was used to detect cell cycle distribution. Further, the distribution of p27 was examined using immunofluorescence. RESULTS: We found that FMNL2 expression was positively associated with Ki67 among collected breast cancer tissues and in TCGA database. Compared to lower proliferative cells MCF7 and T47D, FMNL2 was overexpressed in highly proliferative breast cancer cells MDA-MB-231, BT549 and SUM159, accompanied by reduced levels of p27 and p21, and elevated CyclinD1 and Ki67 expression. FMNL2 silencing significantly inhibited the cell proliferation of MDA-MB-231 and BT549 cells. Meanwhile, FMNL2 overexpression distinctly promoted the cell proliferation of MCF7 cells. Furthermore, FMNL2 suppressed the nuclear levels of p27 and promoted p27 proteasomal degradation in human breast cancer cells. The ubiquitination of p27 was inhibited by FMNL2 silencing in BT549 cells. Besides, p27 silencing markedly elevated Ki67 expression and cell viability, which could be blocked by additionally FMNL2 silencing in MDA-MB-231 and BT549 cells. Furthermore, overexpression of p27WT significantly reversed the increased levels of FMNL2 and Ki67, cell viability and cell cycle progression induced by FMNL2 overexpression in MCF7 cells. More importantly, compared to p27WT group, those effects could be significantly reversed by p27△NLS overexpression. CONCLUSIONS: These results demonstrated that FMNL2 promoted cell proliferation partially by reducing p27 nuclear localization and p27 protein stability in human breast cancer cells, suggesting the pivotal role of FMNL2 in breast cancer progression.

Neoplasias da Mama/genética , Forminas/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Pessoa de Meia-Idade , Transfecção
Am J Transl Res ; 13(1): 1-10, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33527004


Mitochondria, independent double-membrane organelles, are intracellular power plants that feed most eukaryotic cells with the ATP produced via the oxidative phosphorylation (OXPHOS). Consistently, cytochrome c oxidase (COX) catalyzes the electron transfer chain's final step. Electrons are transferred from reduced cytochrome c to molecular oxygen and play an indispensable role in oxidative phosphorylation of cells. Cytochrome c oxidase subunit 6c (COX6C) is encoded by the nuclear genome in the ribosome after translation and is transported to mitochondria via different pathways, and eventually forms the COX complex. In recent years, many studies have shown the abnormal level of COX6C in familial hypercholesterolemia, chronic kidney disease, diabetes, breast cancer, prostate cancer, uterine leiomyoma, follicular thyroid cancer, melanoma tissues, and other conditions. Its underlying mechanism may be related to the cellular oxidative phosphorylation pathway in tissue injury disease. Here reviews the varied function of COX6C in non-tumor and tumor diseases.

Clin Exp Pharmacol Physiol ; 48(2): 279-287, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33030246


Nucleotide metabolism is the driving force of cell proliferation, and thymidylate synthase (TYMS) catalyzes a rate-limiting step in the initial synthesis of nucleotides. Previous studies reported that TYMS activity significantly affected the proliferation of tumour cells. However, the diagnostic and prognostic significance of TYMS expression in breast cancer remains unclear. Here, we used the Breast Cancer Integrative Platform (BCIP) to investigate the relationship between progression and prognosis of breast cancer with TYMS expression, and then verified the database analysis using immunohistochemical staining. Our results indicated TYMS expression was greater in breast cancer than adjacent normal tissues and greater in triple-negative breast cancer (TNBC) than non-TNBC tissues. TYMS expression also had significant positive correlations with histological grade, tumour size, and ER negativity, and PR negativity. The increased copy number of the TYMS gene appears to be the reason for its upregulation in breast cancer. Breast cancer patients with higher TYMS expression had poorer prognosis. Our data suggest that TYMS has potential use as a diagnostic and prognostic marker for breast cancer patients.

Cytoskeleton (Hoboken) ; 77(8): 303-312, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32748571


Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are a large protein complex that is involved in the membrane fusion in vesicle trafficking, cell growth, cytokinesis, membrane repair, and synaptic transmission. As one of the SNARE proteins, SEC22B functions in membrane fusion of vesicle trafficking between the endoplasmic reticulum and the Golgi apparatus, antigen cross-presentation, secretory autophagy, and other biological processes. However, apart from not being SNARE proteins, there is little knowledge known about its two homologs (SEC22A and SEC22C). SEC22B alterations have been reported in many human diseases, especially, many mutations of SEC22B in human cancers have been detected. In this review, we will introduce the specific functions of SEC22B, and summarize the researches about SEC22B in human cancers and other diseases. These findings have laid the foundation for further studies to clarify the exact mechanism of SEC22B in the pathological process and to seek new therapeutic targets and better treatment strategies.

Doença/genética , Transporte Proteico/fisiologia , Proteínas R-SNARE/genética , Humanos
Cancer Sci ; 111(11): 4075-4087, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32860308


Suppressor of Ty 16 (Spt16) is a component of the facilitates chromatin transcription (FACT) complex, which is a histone chaperone and involved in gene transcription, DNA replication, and DNA repair. Previous studies showed that FACT is highly expressed in cancer, and cancer cells are more reliant on FACT than normal cells. However, the relationship between Spt16 and lung cancer remains unclear. In this study, we explored the functions of Spt16 in lung cancer cells. The effects of Spt16 on lung cancer cell proliferation, cell cycle progression, apoptosis, migration, and invasion were examined. We found that knockdown of Spt16 led to obvious decreases of both Rb and MCM7, and further activated the DNA damage response (DDR) pathway. In addition, a novel micro-RNA, miR-1227-5p, directly targeted the 3'-UTR of Spt16 and regulated the mRNA levels of Spt16. Furthermore, we found that CBL0137, the functional inhibitor of FACT, showed similar effects as loss of Spt16. Together, our data indicated that Spt16 is likely to be an essential regulator for lung cancer malignancy and is negatively regulated by miR-1227-5p.

Proteínas de Ciclo Celular/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , MicroRNAs/genética , Fatores de Transcrição/metabolismo , Regiões 3' não Traduzidas , Apoptose/genética , Carbazóis/farmacologia , Ciclo Celular/genética , Cromatina/genética , Cromatina/metabolismo , Dano ao DNA , Progressão da Doença , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/patologia , Gradação de Tumores , Interferência de RNA , Transcrição Genética/efeitos dos fármacos
Ann Noninvasive Electrocardiol ; 21(1): 69-81, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25940734


AIMS: Research related to type 2 diabetes mellitus (DM) and parameters of electrocardiography (ECG) was limited. Patients with and without DM (NDM) were randomly enrolled in a study to exploit the influence of DM on planar QRS and T vectors derived from the Virtual Holter process. METHODS: A total of 216 (NDM) and 127 DM patients were consecutively and randomly recruited. We selected a 1-minute length of ECG, which was scheduled for analysis at 4 AM. After a series of calculating algorisms, we received the virtual planar vector parameters. RESULTS: Patients with DM were elderly (65.61 ± 12.08 vs 59.41 ± 16.86 years, P < 0.001); higher morbidity of hypertension (76.38% vs 58.14%, P < 0.001) and coronary artery disease (44.09% vs 32.41%, P = 0.03); thicker interventricular septum (10.92 ± 1.77 vs 10.08 ± 1.96 mm, P < 0.001) and left ventricular posterior wall (9.84 ± 1.38 vs 9.39 ± 1.66 mm, P = 0.03); higher lipid levels and average heart rate (66.67 ± 12.04 vs 61.87 ± 13.36 bpm, P < 0.01); higher angle of horizontal QRS vector (HQRSA, -2.87 ± 48.48 vs -19.00 ± 40.18 degrees, P < 0.01); lower maximal magnitude of horizontal T vector (HTV, 2.33 ± 1.47 vs 2.88 ± 1.89 mm, P = 0.01) and maximal magnitude of right side T vector (2.77 ± 1.55 vs 3.27 ± 1.92 mm, P = 0.03), and no difference in angle of frontal QRS-T vector (FQRSTA, 32.77 ± 54.20 vs 28.39 ± 52.87 degrees, P = 0.74) compared with patients having NDM. After adjusting for confounding factors, DM was significantly effective on FQRSTA (regression coefficient -40.0, 95%CI -66.4 to -13.6, P < 0.01), HQRSA (regression coefficient 22.6, 95%CI 2.5 to 42.8, P = 0.03), and HTV (regression coefficient 0.9, 95%CI 0.2 to 1.7, P = 0.01). Confounding factors included: sex, 2-hour postprandial blood glucose, smoking, triglyceride, apolipoprotein A, creatinine, left ventricular ejection fraction, and average heart rate. CONCLUSIONS: The risk factors of DM and lipid metabolism abnormality particularly apolipoprotein A significantly modified parameters of virtual planar QRS and T vector, including frontal QRS-T angle.

Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/diagnóstico , Eletrocardiografia Ambulatorial , Idoso , Apoproteína(a)/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Cardiomiopatias Diabéticas/fisiopatologia , Feminino , Humanos , Metabolismo dos Lipídeos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Fatores de Risco