MiR-30a-5p Enhances Cisplatin Sensitivity by Downregulating RIF1 in Ovarian Cancer.

OBJECTIVE: Ovarian cancer (OC) is a common malignant tumor in females with high recurrence and poor prognosis. Cisplatin is commonly used for OC clinical treatment, but its efficacy is usually challenged by the chemotherapy resistance of cancer cells. MicroRNAs (miRNAs), including miR-30a-5p, were identified to modulate drug resistance in numerous tumors. However, molecular mechanisms of miR-30a-5p in OC chemoresistance need more illumination. METHODS: MiR-30a-5p and Rap1 interacting factor 1 (RIF1) expression in OC tissues and cells were measured by qRT-PCR. The IC50 of cisplatin-resistant and cisplatin-sensitive OC cells was assessed by MTT assays. OC cell proliferation, apoptosis and migration were measured by EdU assays, TUNEL staining, and wound healing assays, respectively. The protein levels of EMT markers and RIF1 in OC cells were examined by western blotting. The binding capacity between miR-30a-5p and RIF1 was validated by luciferase reporter assays. RESULTS: Our study disclosed miR-30a-5p as a remarkably lowly-expressed miRNA in OC tissues in comparison to matched noncancerous tissues. Compared to parental cell lines, miR-30a-5p was also greatly downregulated in cisplatin-resistant OC cell lines. Additionally, functional assays indicated that miR-30a-5p suppressed malignant behaviors and cisplatin resistance of OC cells. Further, miR-30a-5p was revealed to target and negatively regulate RIF1 expression in OC. Moreover, it was validated that overexpressing RIF1 reverses the inhibitory influence of miR-30a-5p overexpression on malignant behaviors and cisplatin resistance of OC cells. CONCLUSION: MiR-30a-5p reduced cisplatin resistance in OC through downregulation of RIF1, which may be meaningful for targeting drug-resistant tumors.

Downregulation of ARID1A is correlated with poor prognosis in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the main type of lung cancer and NSCLC patients always have a low 5-year survival rate. It is vital to identify a biomarker for the prognosis of NSCLC patients. AT-rich interaction domain 1a (ARID1A) is a tumor suppressor that is involved in the progression of a variety of tumors. METHODS: The ARID1A protein level in NSCLC tissues and paracancerous normal lung (PCNL) tissues were detected with immunohistochemistry (IHC) and western blotting (WB). The χ2 test and Spearman's rank correlation analysis were carried out to examine the association between ARID1A expression and the clinicopathological features of NSCLC. The Kaplan-Meier method and log-rank test were used to compare overall survival (OS) in the ARID1A low expression group and the ARID1A high expression group. RESULTS: The results of WB and IHC demonstrated that the ARID1A protein level was significantly reduced in NSCLC tissues compared with PCNL tissues (P<0.05). The low expression of ARID1A in NSCLC tissues was significantly associated with poor differentiation (P=0.005), smoking (P<0.001), lymphatic invasion (P=0.013), distant metastasis (P=0.010), and high TNM stage (P=0.001). The overall five-year survival rate of NSCLC patients was lower in the ARID1A low expression group than in the ARID1A high expression group. Multivariate analysis showed that the expression of ARID1A had an independent prognostic impact on OS (P=0.024). CONCLUSIONS: ARID1A may be a novel biomarker for predicting the prognosis of NSCLC patients.

Analysis of the changes in Th9 cells and related cytokines in the peripheral blood of spontaneous urticaria patients.

Spontaneous urticaria (SU) is characterized by immune deregulation of mast cells and T helper (Th) cells. Th9 cells, a subset of Th cells, serve a key role in initiating mast cell accumulation and activation. To understand the role of Th9 cells in the pathogenesis of SU, the authors conducted a control study of 28 patients with acute SU (ASU) and chronic SU (CSU) and 28 healthy controls. The percentage of Th9 cells in peripheral blood was assessed using flow cytometry and levels of Th9 related serum cytokines including interleukin (IL)-4, IL-9, IL-17A, IL-33, IL-1ß and transforming growth factor-ß1 (TGF-ß1) using Luminex 200. ASU patients exhibited higher percentages of Th9 cells and increased serum levels of cytokines IL-9, IL-4 and TGF-ß1 compared to healthy controls. In addition, high mRNA expression of the PU.1 transcription factor was observed in ASU patients. However, the percentage of Th9 cells was similar between patients with CSU and healthy controls. Furthermore, the percentage of Th9 cells demonstrated a positive correlation with IL-4 and IL-9 levels in the peripheral blood of ASU patients, but not with disease severity. The current findings suggested that the numbers of Th9 cells increased in ASU patients and indicated its novel role in the pathogenesis of ASU.

Antimicrobial peptide LL-37 along with peptidoglycan drive monocyte polarization toward CD14(high)CD16(+) subset and may play a crucial role in the pathogenesis of psoriasis guttata.

The human cathelicidin LL-37 peptide is overexpressed in psoriasis and has been demonstrated to be a multifunctional modulator of innate immune response elements, including monocytes. Monocytes, categorized into three populations based on the cell surface expression of CD14 and CD16, are activated in psoriasis guttate and are commonly triggered by streptococcal infections. Peptidoglycan (PGN) is a major cell-wall component of streptococcus, and an increasing number of PGN-containing cells have been detected in psoriasis. Since there are independent reports of both PGN and LL-37 influencing monocytes, we tried to evaluate the effect of human LL-37 on PGN-induced monocyte activity and differentiation and subsequently studied their correlation with the pathogenesis of psoriasis guttate. The results revealed that monocytes from the peripheral blood of healthy individuals resulted in their polarization toward the CD14(high)CD16(+) subset, when cultured with PGN in the presence of the LL-37 peptide. This peptide further induced PGN-driven differentiated monocytes into immature dendritic cells (iDC), as evident by the increased expression of CD1a, CD86, and HLA-DR markers, resulting in the induction of T cell proliferation and Th17 polarization. Furthermore, our data suggested that psoriasis guttata patients have significantly higher percentages of CD14(high)CD16(+) monocytes as well as circulating levels of LL-37, soluble form of triggering receptor expressed on myeloid cells (sTREM-1) levels, and anti-streptolysin O (ASO) levels, as compared to healthy controls. Psoriasis guttata patients also showed a positive correlation between the percentage of CD14(high)CD16(+) monocytes and the serum levels of sTREM-1 as well as the Psoriasis Area and Severity Index (PASI) scores. Therefore, we concluded that LL-37 in synergy with PGN directs monocyte polarization and differentiation into a proinflammatory phenotype, which might play a crucial role in the pathogenesis of psoriasis.