MiR-491 suppresses migration and invasion via directly targeting TPX2 in breast cancer.

OBJECTIVE: Breast cancer (BC) is one of the primary causes of tumor-related female mortalities. Although in recent years, we have made great progress in the systemic therapy and earlier diagnosis for BC patients, recurrence or distant metastasis remains leading obstacles for the successful therapy of BC. Therefore, a comprehensive understanding of the molecular mechanism underlying the progression may be crucial in developing an effective strategy against BC. The current research aimed to explore the expressions, functions and molecular mechanism of microRNA-491 (miR-491) in BC. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the level of miR-491 expression in 52 pairs of BC tissues and para-cancerous specimens, and the relation between miR-491 level and the clinical features of BC patient prognosis was analyzed. Transwell invasion and migration assays were conducted to determine whether miR-491 had effects on the regulation of BC metastasis. Potential target genes of miR-491 were found out using TargetScan to explore the molecular functions of miR-491 in inhibiting breast cancer cell invasion and migration. To elucidate the mechanism of TPX2 in suppressing cell invasion and migration medicated by miR-491in breast cancer, we further transfected TPX2 siRNAs into MCF-7 cells to delete endogenous TPX2, along with the transfections with miR-491 inhibitor into MCF-7 cell lines. RESULTS: The findings demonstrated that miR-491 expressions were significantly decreased in BC tissues and cells. The miR-491 restoration suppressed the invasion and migration of BC cells. In addition, we identified the targeting protein for Xklp2 (TPX2) as a direct target of miR-491 in BC. The knockdown of TPX2 markedly reversed miR-491-medicated inhibition of cell invasion and migration in BC cell lines. CONCLUSIONS: In short, all the results suggested that miR-491 functioned as a tumor suppressor by targeting TPX2 in BC and the miR-491 restoration may be an effective therapy for the BC treatment in the future.

Systemic lupus erythematosus with and without a family history: a meta-analysis.

Objective The objective of this paper is to investigate the association of clinical manifestations and laboratory parameters between familial systemic lupus erythematosus (SLE) and sporadic SLE. Methods All relevant literature was retrieved from the PubMed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) databases. The qualities of these studies were evaluated using a modified version of the Newcastle-Ottawa scale. The characteristics and clinical manifestations of involved individuals were extracted from each study. Pooled odds ratio (OR) was calculated using the random effects-method, and the heterogeneity between studies was quantified using the I2 statistic. Results Of 330 studies identified by the search strategy, six were included in this review. In total, 733 cases were familial SLE and 1405 were sporadic SLE. Analysis revealed that photosensitivity, nephritis and thrombocytopenia were negatively associated with familial SLE, with OR (95% CI) values of 0.73 (0.60-0.89), 0.72 (0.59-0.88) and 0.75 (0.57-0.98), respectively. Conclusions Photosensitivity, thrombocytopenia and renal involvement could be more common in non-familial SLE, which should be further confirmed by well-designed studies with large populations.

The association of serum anti-ribosomal P antibody with clinical and serological disorders in systemic lupus erythematosus: a systematic review and meta-analysis.

OBJECTIVE: Anti-ribosomal P (anti-P) antibody is a serological specific marker of systemic lupus erythematosus (SLE). The aim of this study is to investigate the association of this antibody with clinical and serological disorders in SLE. METHODS: All relevant literature was retrieved from PubMed, EMBASE, Web of Science and CNKI databases. The qualities of these studies were evaluated using a modified version of the Newcastle-Ottawa scale. The associations of anti-P antibody with clinical and serological disorders were determined by the pooled odds ratio (OR) and the confidence interval (CI) calculated using meta-analysis with the Mantel-Haenszel method. RESULTS: Sixteen cohort studies with 2355 patients were included in this study. Malar rash, oral ulcer and photosensitivity were strongly associated with serum anti-P antibody, with OR (95% CI) values of 2.05 (1.42-2.92), 1.49 (1.05-2.13) and 1.44 (1.08-1.91), respectively. Arthritis and renal involvement were not associated with anti-P antibody, whereas a high heterogeneity was observed due to ethnicity and publication bias, respectively. Neuropsychiatric SLE (NPSLE), hepatic involvement, anti-dsDNA, anti-Sm and anti-cardiolipin antibodies (aCL) were observed more frequently in anti-P positive patients than in negative patients. Studies on hepatic involvement showed a low precision with substantially broad CI (2.56-11.2). A high heterogeneity presented among studies on NPSLE, anti-Sm and aCL. CONCLUSIONS: Anti-P antibody is significantly associated with malar rash, oral ulcer, photosensitivity and serum anti-dsDNA antibody, and potentially associated with NPSLE, hepatic damage, serum anti-Sm and aCL.

The association of anti-annexin1 antibodies with the occurrence of skin lesions in systemic lupus erythematosus.

Anti-annexin1 antibodies are associated with the subtypes of cutaneous lupus and are elevated in systemic lupus erythematosus (SLE) patients. In this study, we investigated the correlation of this antibody with the incidence of SLE skin lesions. The presence of anti-annexin1-IgG and-IgM determined by Western blot was no different among healthy controls and SLE patients with and without skin lesions. Serum levels of anti-annexin1-IgG and -IgM measured by enzyme-linked immunosorbent assay were comparable between patients with and without skin lesions, whereas anti-annexin1-IgM was lower in SLE patients than in healthy controls. Annexin1 was abundantly detected in each epidermal layer in lupus lesional skin. Additionally, anti-annexin1-IgG was higher in SLE patients with arthritis and negatively correlated with white blood cells (WBC). Anti-annexin1-IgM was higher in patients with antinuclear antibody (ANA)-positive sera, and was positively related to hemoglobin and total serum IgM. Collectively, anti-annexin1 antibodies are not related to the incidence of skin lesions in SLE, and annexin1 abundantly distributes in epidermis in lesional skin.

The gender disparity of immunoreactants in lesional skin of lupus erythematosus patients.

OBJECTIVES: The immunoreactants detected by direct immunofluorescence (DIF) from the skin of patients with lupus erythematosus (LE) were related to disease subtypes and skin morphology. Male patients presented more frequently with discoid rashes and females with malar rashes. We investigated the differences in immunoreactants in skin lesions between male and female LE patients. METHODS: The DIF records of 186 LE patients were reviewed and analysed. RESULTS: Among 186 patients (133 female and 53 male), 54 had cutaneous LE (CLE) and 132 had systemic LE (SLE). In the CLE group, eight of 33 (24.2%) women were DIF+ versus nine of 21(42.9%) men (p=0.23). In the SLE group, 49 of 100 (49%) women were DIF+ versus 17 of 32 (53.1%) men (p=0.84). The p-value was 0.01 when comparing DIF incidence between female CLE and SLE patients. IgM and complement component 3 (C3) were present in 84.2% and 52.6% of DIF+female patients, respectively, and both were comparable between genders (p>0.05). However, IgG was observed only in eight of 57 female patients, and in 10 of 26 male patients (p=0.02). Among DIF+CLE patients, IgG was detected in none of the eight female versus three of nine male patients. CONCLUSIONS: Detection of immunoreactants in skin had no gender bias in CLE or SLE, but among women, it was probably lower in CLE than SLE. IgM and C3 were the most frequent immunoreactants in skin with no gender disparity, whereas IgG in female patients was lower than in males.