Circ_0091581 Promotes the Progression of Hepatocellular Carcinoma Through Targeting miR-591/FOSL2 Axis.

BACKGROUND: Circular RNAs (circRNAs) have shown crucial regulatory roles in cancer biology. We aimed to uncover the role and underlying mechanism of circ_0091581 in hepatocellular carcinoma (HCC) progression. METHODS: The abundance of circ_0091581, microRNA-591 (miR-591) and FOS like 2, AP-1 transcription factor subunit (FOSL2) was measured by quantitative real-time polymerase chain reaction. Cell viability, colony formation ability, and invasion ability were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and transwell invasion assay. The migration ability was analyzed by transwell migration assay and wound healing assay. Flow cytometry was used to evaluate the cell cycle and apoptosis of HCC cells. The interaction between miR-591 and circ_0091581 or FOSL2 was predicted by Circular RNA Interactome database or TargetScan database and confirmed by dual-luciferase reporter assay and RNA immune co-precipitation assay. FOSL2 protein expression was measured by Western blot assay. Xenograft tumor assay was conducted to analyze the role of circ_0091581 in HCC tumor growth in vivo. RESULTS: Circ_0091581 was highly expressed in HCC tissue samples and cell lines in contrast to that in adjacent normal tissue samples and THLE-2 cell line. Circ_0091581 accelerated the viability, colony formation, metastasis, and cell cycle, while it impeded the apoptosis of HCC cells. MiR-591 bound to circ_0091581, and circ_0091581 knockdown-mediated effects in HCC cells were largely overturned by miR-591 silencing. FOSL2 was a target of miR-591, and FOSL2 overexpression largely reversed miR-591 accumulation-induced influences in HCC cells. FOSL2 protein expression was down-regulated by circ_0091581 silencing, and the addition of miR-591 inhibitor partly recovered the expression of FOSL2 in HCC cells. Circ_0091581 interference notably suppressed HCC tumor growth in vivo. CONCLUSION: Circ_0091581 acted as an oncogene to enhance the viability, colony formation, metastasis and cell cycle and inhibit the apoptosis of HCC cells through targeting miR-591/FOSL2 axis.

Prognostic value of lymphocyte to monocyte ratio in pancreatic cancer: a systematic review and meta-analysis including 3338 patients.

BACKGROUND: Recently, reports have classified lymphocyte to monocyte ratio (LMR) as an effective indicator for predicting the prognosis of pancreatic cancer. Nevertheless, the prognostic value of LMR for pancreatic cancer remains controversial. Through meta-analysis, this work intends to evaluate the potential prognostic role of pretreatment LMR in patients diagnosed with pancreatic cancer. METHODS: We reviewed and extracted eligible articles from Web of Science, PubMed, Cochrane Library, and Embase. A meta-analysis was conducted using hazard ratio (HR) and 95% confidence intervals (CIs) to assess the comparison between pretreatment LMR and overall survival (OS) and disease-free survival/recurrence-free survival/time to progression (DFS/RFS/TTP). RESULTS: In total, 11 studies (16 cohorts) including 3338 patients diagnosed with pancreatic cancer (PC) were enrolled in our meta-analysis. Notably, we revealed that high pretreatment LMR predicted better overall survival (OS) (HR = 0.68, 95% CI 0.58-0.80, P < 0.001, I-squared = 69.3%, Ph < 0.001) and DFS/RFS/TTP (HR = 0.55, 95% CI 0.31-0.96, P = 0.037, I-squared = 89.9%, Ph < 0.001) in patients with pancreatic cancer. Further, through subgroup analyses, we showed that high pretreatment LMR was significantly associated with the favorable OS regardless of ethnicity, study design, treatment method, variable type, the cut-off value for LMR, and disease stages of I-IV and III-IV. CONCLUSION: The findings from our study suggest that high pretreatment LMR is associated with better OS and DFS/RFS/TTP in patients diagnosed with pancreatic cancer. As such, it can potentially serve as a novel prognostic biomarker for patients with pancreatic cancer.

Clinicopathological and prognostic value of preoperative lymphocyte to monocyte ratio for hepatocellular carcinoma following curative resection: A meta-analysis including 4,092 patients.

BACKGROUND: Previous studies have reported that lymphocyte-to-monocyte ratio (LMR) had novel prognostic value in hepatocellular carcinoma (HCC). The purpose of this meta-analysis was to synthetically evaluate the prognostic role of preoperative LMR in HCC patients following curative resection. METHODS: Eligible studies were acquired through searching Pubmed, Web of Science, Cochrane Library and EMbase update to September 2019. Merged hazard ratios (HRs) and 95% confidence intervals (CIs) were applied as effect sizes. RESULTS: A total of ten studies containing 4,092 patients following liver resection were enrolled in this meta-analysis. The pooled results demonstrated that preoperative elevated LMR indicated superior survival outcome (HR: 0.58, 95% CI: 0.34-0.96, P = .035) and recurrence-free survival (RFS)/disease-free survival/time to recurrence (HR = 0.76, 95% CI: 0.58-0.98, P = .034). The significant prognostic role of preoperative LMR was detected in the subgroup of all publication year, country of origin, sample sizes <300, TNM stage of I-IV and LMR cut-off value ≤4. Furthermore, high LMR was significantly associated with male, high AFP, large tumor size, incomplete tumor capsule, advanced TNM stage and BCLC stage, and presence of PVTT. CONCLUSION: Elevated preoperative LMR indicated superior survival outcome in HCC patients following curative resection, and might serve as a novel prognostic biomarker.

Meta-analysis of the prognostic value of pretreatment serum ferritin in hepatobiliary and pancreas (HBP) cancers.

BACKGROUND AND OBJECTIVES: Studies have shown that serum ferritin (SF) has unfavourable prognostic value in hepatobiliary and pancreas (HBP) cancers. This meta-analysis aimed to comprehensively assess the prognostic role of pretreatment SF in patients with HBP cancers. METHODS: Eligible studies published before January 2020 were obtained through a comprehensive search in the PubMed, Web of Science, Cochrane Library and EMBASE databases. Pooled HRs and 95% CIs were then employed as effect sizes. RESULTS: Seven studies comprising 1244 patients were pooled. Elevated pretreatment SF was associated with worse overall survival (OS) (HR 1.60, 95% CI 1.36 to 1.88, p<0.001) and recurrence-free survival/progression-free survival/time to recurrence (HR 1.70, 95% CI 1.15 to 2.52, p=0.008). Significant prognostic value of elevated pretreatment SF on OS was detected in the subgroups regardless of the cancer type, race, SF cut-off value, tumour-node-metastasis stage and Newcastle-Ottawa Scale score. CONCLUSION: Elevated pretreatment SF was associated with worse survival outcome of patients with HBP cancers. As such, it may serve as a novel prognostic biomarker for HBP cancers.

circRPS16 Promotes Proliferation and Invasion of Hepatocellular Carcinoma by Sponging miR-876-5p to Upregulate SPINK1.

The roles of serine protease inhibitor Kazal type 1 (SPINK1) in multiple types of cancers have been significantly documented. However, its specific roles in hepatocellular carcinoma (HCC) remain to be investigated. This study found that SPINK1 is upregulated in HCC and its upregulation correlates with poor prognosis. Besides, functional assays revealed that SPINK1 promotes cell proliferation, cell cycle, and invasion in vitro. Through bioinformatics analysis, we speculate that circRPS16 regulates SPINK1 expression by sponging miR-876-5p. This was further verified by the dual-luciferase reporter and fluorescent in situ hybridization (FISH) assays. Subsequently, rescue assays verified that circRPS16 promotes cell proliferation, cell cycle, and invasion through miR-876-5p. Importantly, silencing circRPS16 inhibited tumor growth by downregulating SPINK1 expression in vivo. Collectively, our results confirm that SPINK1 is a downstream target of circRPS16. Besides, circRPS16 and SPINK1 are oncogenic factors in HCC progression; they provide novel diagnostic and therapeutic targets for HCC patients.