Cutaneous melanoma is very aggressive and results in high mortality rates for cancer patients. Determining molecular targets is important for developing novel therapies for cutaneous melanoma. Cell division cycle associated 8 (CDCA8) is a putative oncogene that is upregulated in multiple types of cancer. The present study aimed to examine the role of CDCA8 in cutaneous melanoma, with a focus on the association of its expression to prognosis and metastasis. First, the mRNA expression of CDCA8 in cutaneous melanoma tissues was investigated using the ONCOMINE and Gene Expression Omnibus (GEO) databases. Furthermore, the relationship between the expression of CDCA8 and cutaneous melanoma patient survival was analyzed using a Kaplan-Meier plot and Log Rank test. In addition, the effects of CDCA8 on proliferation, migration and invasion of cutaneous melanoma cell lines were investigated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Cell Counting kit-8, colony formation assay, wound healing and Matrigel assay. Finally, the expression levels of key proteins related to the Rho-associated coiled-coil-containing protein kinase (ROCK) signaling pathway were measured by western blot assay. The results demonstrated that CDCA8 was overexpressed in cutaneous melanoma tissues and cells lines compared with normal tissues, and high expression of CDCA8 was significantly associated with poorer prognosis in patients with cutaneous melanoma. In in vitro experiments, CDCA8 knockdown inhibited A375 and MV3 cell proliferation, migration and invasion. In addition, CDCA8 knockdown reduced the phosphorylation levels of ROCK1 and myosin light chain, two downstream effector proteins of the ROCK pathway. In summary, the present findings suggested that CDCA8 may be a promising therapeutic target for the treatment of cutaneous melanoma.
Summary Background The protein kynureninase (KYNU) has recently been reported to participate in the pathological processes of various diseases. Aim To explore the expression and the biological function of KYNU in cutaneous squamous cell carcinoma (cSCC). Methods Expression of KYNU in cSCC cell lines and tissues was firstly evaluated based on the Gene Expression Omnibus and the Oncomine databases. Quantitative reverse transcription–PCR was performed to determine the mRNA expression of KYNU in cSCC cell lines. Small interfering RNA (siRNA) was used for silencing KYNU. The effect of KYNU on the growth and motility of cSCC cells was determined by cell counting kit‐8, wound‐healing and Transwell assays, and western blotting was used to determine the protein expression of KYNU, AKT, phosphoinositide 3‐kinase (PI3K), phosphorylated (p)‐AKT and p‐PI3K. Results KYNU was significantly upregulated in cSCC tissues and cell lines. Knockdown of KYNU using siRNA noticeably suppressed the proliferation, migration and invasion ability of SCL‐1 cells (P < 0.01). Western blotting revealed that phosphorylation of AKT and PI3K was markedly inhibited after silencing KYNU. The ratios of p‐AKT/AKT and p‐PI3K/PI3K were significantly decreased in the si‐KYNU group compared with the control group. Conclusion Depletion of KYNU could inhibit the growth of cSCC cells, possibly through modulating PI3K/AKT pathway. These data indicate that KYNU takes a key part in the malignant progression of cSCC, and could be considered as a promising therapeutic target for cSCC treatment.
Introduction: Many studies have explored the imaging characteristics of patients with neurosyphilis, but no systematic study has been made on the neuroimaging changes after antisyphilitic treatment. The purpose of this study was to examine neuroimaging differences before and after treatment, comparing patients with asymptomatic and symptomatic neurosyphilis. Methods: A total of 102 patients with neurosyphilis, including 60 cases of symptomatic neurosyphilis and 42 cases of asymptomatic neurosyphilis, were identified between December 2012 and June 2019. Their demographics, medical histories, serological tests of peripheral blood and cerebrospinal fluid, and especially neuroimaging features before and after antisyphilitic treatment were collected and analyzed. Results: The patients presented with variable clinical and neuroimaging features, including cerebral infarction or hemorrhage, atrophy, demyelination, arteritis, encephalitis, and hippocampal sclerosis. A total of 29 neuroradiological re-examinations were performed in 19 patients treated with anti-syphilitic medicine. The results indicated that some patients still presented neuroradiological progression after treatment, including 42.1% showing infarction lesions, 47.4% mild to severe brain atrophy, and 15.8% white matter demyelination. Conclusion: The clinical and neuroimaging features of neurosyphilis patients are diverse, and their follow-up neuroimaging continued to show progression even with standardized treatment.
Background Bowen's disease is a cutaneous squamous cell carcinoma (CSCC) in situ. If left untreated, BD may progress to invasive CSCC. CSCC is one of the most common cutaneous carcinoma in the elderly and the advanced, metastasis CSCC usually have a poor outcomes. However, the mechanisms of invasion and metastasis from Bowen’s disease to CSCC is complicated and still unclear. Objectives The aim of this study was to explore the biomarkers and molecular alterations in Bowen’s disease development process via analyzing the proteomics changes in tissues of CSCC, Bowen disease and healthy skin. Methods A total of 7 individuals with CSCC (5 for proteomics study and 2 for validation), 7 individuals with Bowen disease (5 for proteomics study and 2 for validation) and 7 healthy controls (5 for proteomics study and 2 for validation) presented to the Department of Dermatology, Yijishan Hospital, the First Affiliated Hospital of Wannan Medical College between January 2021 and December 2021 were enrolled. The proteomics analysis was performed to screen differentially expressed proteins/gens (DEPs/DEGs) in the lesions of CSCC, Bowen disease and healthy skin tissues. The transcriptomic data (GSE32628) of CSCC was selected and downloaded from the GEO database. The common DEGs in our proteomics results and GSE32628 between CSCC and healthy skin tissues were selected. And then, the common DEGs which significantly up or down-regulated between CSCC and Bowen disease in our proteomics results were further screened to identify using Western blot methods in the validation group. CSCC A431 cells were transfected with SERPINB1 small interfering RNA (si-SERPINB1) or small interfering RNA negative control (si-NC). To explore the effect of SERPINB1 silencing on migration and invasion ability of A431 cells. Results A total of 501 proteins were differentially expressed between the CSCC and healthy skin tissues, with 332 up-regulated and 169 down-regulated at least 1.5-fold with a P value < 0.05. These DEPs involved multiple biological functions such as protein binding process, immune, inflammation, ribosome, protein digestion and absorption, ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway and others. A total of 20 common DEGs (COL3A1, LUM, TNC, COL1A1, ALDH3A2, FSCN1, SERPINB4, SERPINB1, CD36, COL4A1, CSTB, GPX3, S100A7, ACTN1, SERPINB3, S100A8, RAB31, STAT1, SPRR1B, S100A9) between CSCC and healthy skin tissues in GSE32628 and our proteomics results were found. Besides, the proteins of TNC, FSCN1, SERPINB1, ACTN1 and RAB31 in CSCC were significantly up-regulated, while COL3A1, COL1A1 and CD36 were significantly down-regulated relative to Bowen disease in proteomics results. These proteins were mainly involved in multiple pathways, including Focal adhesion, ECM-receptor interaction, Human papillomavirus infection, PI3K-Akt signaling pathway, PPAR signaling pathway, AMPK signaling pathway and others. These eight proteins were selected for further validation. According to the Western blotting analysis, when compared with the Bowen disease and healthy skin tissues, we found that the relative expression levels of TNC, FSCN1, SERPINB1, ACTN1 and RAB31 in the CSCC were significantly increased, while COL1A1 and CD36 were significantly decreased, and the differences were statistically significant (P < 0.05). Furthermore, the relative expression levels of TNC, FSCN1, SERPINB1 in the Bowen disease were also significantly increased, while the COL3A1 were also significantly decreased relative to the healthy control. SERPINB1 siRNA inhibited the expression of SERPINB1 at mRNA and protein levels in the A431 cells. After interfering with the expression of SERPINB1, the migration and invasion ability in the A431 cells were significantly decreased (P < 0.05). Conclusions This study highlights that eight proteins, TNC, FSCN1, SERPINB1, ACTN1, RAB31, COL3A1, COL1A1, CD36, were significantly associated with the mechanisms of invasion and metastasis in Bowen’s disease.
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