Circ_0000263 facilitates the proliferation and inhibits the apoptosis of cervical cancer depending on the regulation of miR-1179/ABL2 axis.

Circular RNA (circRNA) has been reported to participate in the progression of cervical cancer (CC). Studies on the role and mechanism of circ_0000263 in CC are limited, and more studies are needed. The expression of circ_0000263, microRNA (miR)-1179 and ABL proto-oncogene 2 (ABL2) mRNA in tissues and cells was analyzed by quantitative real-time PCR. The proliferation and apoptosis of CC cells were determined using cell counting kit 8 assay, Edu assay, colony formation assay and flow cytometry. The protein expression of proliferation markers, apoptosis markers and ABL2 was detected by western blot analysis. The interaction between RNAs was estimated via dual-luciferase reporter assay. Xenograft models were applied to explore the effect of circ_0000263 knockdown on CC tumorigenesis. Circ_0000263 was highly expressed in CC tumor tissues. Silencing of circ_0000263 suppressed CC cell proliferation and increased apoptosis. Circ_0000263 served as a sponge for miR-1179, and miR-1179 inhibitor reversed the regulation of si-circ_0000263 on CC cell proliferation and apoptosis. ABL2 could be targeted by miR-1179, and circ_0000263 could sponge miR-1179 to regulate ABL2. Overexpression of ABL2 reversed the anti-proliferation and pro-apoptosis roles of miR-1179 in CC cells. In addition, circ_0000263 knockdown reduced CC tumor growth by miR-1179/ABL2 axis. In brief, the results demonstrated that circ_0000263 exerted an oncogene role in CC, which suggested that circ_0000263 might be a promising therapeutic target for CC.

Circ_0061140 Contributes to the Malignant Progression in Ovarian Cancer Cells by Mediating the RAB1A Level Through Sponging miR-361-5p.

Ovarian cancer (OC) progression is related to many functional molecules, including circular RNAs (circRNAs). Hsa_circ_0061140 (circ_0061140) promoted cell growth and metastasis in OC. The aim of this study was to explore a specific functional mechanism of circ_0061140. Reverse transcription-quantitative polymerase chain reaction was performed for expression analysis of circ_0061140, microRNA-361-5p (miR-361-5p), and Ras-like protein in rat brain 1A (RAB1A). Cell proliferation was determined using Cell Counting Kit-8 assay, EdU assay, and colony formation assay. The migration and invasion were assessed through transwell assay. Tube formation assay was used for angiogenesis analysis. Cell apoptosis was evaluated using flow cytometry. The protein levels of epithelial-to-mesenchymal transition (EMT) markers and RAB1A were detected via western blot. Target analysis was performed by dual-luciferase reporter assay and RNA immunoprecipitation assay. In vivo research was conducted using xenograft model. The circ_0061140 level was upregulated in OC samples and cells. Downregulation of circ_0061140 impeded proliferation, migration, invasion, EMT, and angiogenesis of OC cells. Circ_0061140 directly interacted with miR-361-5p to act as a miRNA sponge. The miR-361-5p inhibition reversed the si-circ_0061140-induced anti-tumor function in OC cells. RAB1A was a downstream target of miR-361-5p, and miR-361-5p served as a tumor repressor in OC via inhibiting the level of RAB1A. Circ_0061140 could increase the RAB1A expression by sponging miR-361-5p in OC cells. Circ_0061140 also facilitated tumorigenesis in vivo through targeting the miR-361-5p/RAB1A axis. All results demonstrated that circ_0061140 promoted OC development by inhibiting miR-361-5p to upregulate the expression of RAB1A.

HNRNPL Is Identified and Validated as a Prognostic Biomarker Associated with Microsatellite Instability in Human Gastric Cancer.

Microsatellite instability (MSI) is emerging as a promising subtype related to immunotherapy in gastric cancer (GC). However, the underlying mechanism between MSI and microsatellite stability (MSS) remains unclear. In this study, we conducted a weighted gene co-expression network analysis and found that the expression of heterogeneous nuclear ribonucleoprotein L (HNRNPL) was significantly increased in MSI GC compared with MSS GC. This finding was further validated in public GC cohorts and commercialized human GC tissue microarray. The significant negative correlation with the expression of mismatch repair protein mutL homolog 1 (MLH1) may be one of the potential mechanisms for the upregulation of HNRNPL expression in MSI GC (R = -0.689, p = 8.59e-11). In addition, HNRNPL expression was markedly upregulated in GC tissues compared with adjacent normal tissues. High HNRNPL expression also predicted a poor prognosis in GC patients. Finally, gene set enrichment analysis revealed that high HNRNPL MSI GC samples were highly positive associated with the biological functions of inflammation and cell proliferation, such as interferon gamma response, MYC targets, E2F targets, and G2/M checkpoints. In conclusion, HNRNPL could be a new MSI-associated prognostic biomarker in GC and could be a new target for the MSI GC treatment.

High C-Reactive Protein to Albumin Ratio Predicts Inferior Clinical Outcomes in Extranodal Natural Killer T-Cell Lymphoma.

OBJECTIVE: The prognostic value of C-reactive protein to albumin ratio (CAR) has been identified in several cancers but not in extranodal natural killer T-cell lymphoma (ENKTL) as yet. We aimed to evaluate the prognostic value of CAR in ENKTL. METHODS: A retrospective study with 246 patients with ENKTL was performed to determine the prognostic value of pretreatment CAR and examine the prognostic performance of CAR incorporating with International Prognostic Index (IPI) or natural killer/T-cell lymphoma prognostic index (NKPI) by nomogram. RESULTS: The Cox regression analyses showed that high CAR (>0.3) independently predicted unfavorable progression-free survival (PFS, P = .011) and overall survival (OS, P = .012). In the stratification analysis, the CAR was able to separate patients into different prognoses regarding both OS and PFS in Ann Arbor stage I+II as well as III+IV, IPI score 0 to 1, and NKPI score 1 to 2 subgroups (all P < .05). Additionally, the predictive accuracy of the IPI-based nomogram incorporating CAR, albumin to globulin ratio (AGR), and IPI for OS and PFS appeared to be lower than the NKPI-based nomogram incorporating CAR, age, AGR, extranodal site, and NKPI. CONCLUSION: Pretreatment CAR is a simple and easily accessible parameter for independently predicting OS and PFS in patients with ENKTL.

Cyclooxygenase-2 polymorphisms and bladder cancer risk: a meta-analysis based on case-control studies.

The current meta-analysis incorporating 15 case-control studies involving 4,138 cases and 4,269 controls was performed on the basis of a systematical search in electronic databases for a more precise estimation on the associations of three common polymorphisms -765 G>C (rs20417), -1195G>A (rs689466) and +8473 C>T (rs5275) in Cyclooxygenase-2 (Cox-2) gene with the susceptibility to bladder cancer. The results showed that there was a significant association between rs5275 polymorphism and bladder cancer risk (C vs. T; OR=0.84; CC vs. TT: OR=0.76), especially among Chinese (CC vs. TC+TT: OR=0.48) and American (C vs. T; OR=0.83; TC vs. TT: OR=0.73; CC+TC vs. TT: OR=0.73). and the rs20417 polymorphism was significantly associated with an increased risk of bladder cancer among Chinese (C vs. G: OR=1.46; GC vs. GG: OR=1.49; CC+GC vs. GG: OR=1.51) and Indian (GC vs. GG: OR=1.63; CC+GC vs. GG: OR=1.46), but a reduced risk among American (C vs. G: OR=0.81; GC vs. GG: OR=0.76; CC+GC vs. GG: OR=0.76). Additionally, we found that the rs689466 polymorphism was associated with a decreased risk of bladder cancer in Indian (GA vs. GG: OR=0.68; AA vs. GG: OR=0.39).The present meta-analysis suggests that Cox-2 rs5275 polymorphism may contribute to the risk of bladder cancer, particularly among Chinese and American. The rs20417 polymorphism may play a protective role in the development of bladder cancer in Indian and Chinese but act as a risk factor among American, while the rs689466 polymorphism was more likely to be associated with a decreased risk of bladder cancer in Indian.