Effects of genetic polymorphisms of LINC-PINT gene on liver cancer susceptibility in the Chinese Han population.

Objective: Liver cancer (LC) is the most common cause of cancer mortality. This study aimed to explore the impact of LINC-PINT polymorphisms on LC. Materials & methods: The authors recruited 591 LC patients and 592 healthy controls. The association between LINC-PINT polymorphisms and susceptibility to LC was determined by logistic regression analysis. Results: The authors found that rs157916 and rs16873842 reduced susceptibility to LC. rs157916 decreased LC risk in patients aged <55 years, nondrinkers and those with BMI <24. rs16873842 had a protective role against LC in patients aged ≥55 years, women, nonsmokers and those with BMI ≥24. rs7801029 decreased LC risk in patients with BMI <24. rs28662387 increased LC risk in women. Conclusion: LINC-PINT polymorphisms exert a protective effect against LC.

Contribution of PNPLA3 gene polymorphisms to hepatocellular carcinoma susceptibility in the Chinese Han population.

OBJECTIVES: The purpose of this study was to investigate the association of PNPLA3 single nucleotide polymorphisms (SNPs) (rs738409 C > G, rs3747207 G > A, rs4823173 G > A, and rs2896019 T > G) with hepatocellular carcinoma (HCC) susceptibility. METHODS: This case-control study included 484 HCC patients and 487 controls. Logistic regression analysis was performed to study the associations of PNPLA3 gene polymorphisms with HCC susceptibility, and odds ratios with their corresponding 95% confidence intervals were calculated to evaluate these correlations. RESULTS: In the overall analysis, we found that the G allele (OR = 1.25, 95% CI = 1.04-1.50, p = 0.018, false discovery rate (FDR)-p = 0.035) and GG genotype (OR = 1.59, 95% CI = 1.06-2.39, p = 0.024, FDR-p = 0.048) of rs2896019 were significantly associated with increased HCC susceptibility. In stratified analysis, we found that all four SNPs were related to increased HCC susceptibility in subjects aged > 55 years. In haplotype analysis, the GAAG haplotype was significantly associated with increased HCC susceptibility (OR = 1.25, 95% CI = 1.03-1.53, p = 0.023, FDR-p = 0.046). Besides, we noticed that rs738409 was significantly correlated with alpha-fetoprotein (AFP) (p = 0.007), and HCC patients with the GG genotype had a higher level of AFP. CONCLUSIONS: Our study suggested that PNPLA3-rs2896019 was significantly associated with an increased susceptibility to HCC.

Circular RNA Fibroblast Growth Factor Receptor 1 Promotes Pancreatic Cancer Progression by Targeting MicroRNA-532-3p/PIK3CB Axis.

OBJECTIVE: The aim of the study is to explore the contribution and mechanism of circular RNA fibroblast growth factor receptor 1 (circFGFR1) in pancreatic ductal adenocarcinoma (PDAC) progression. METHODS: Expressions of circFGFR1, microRNA (miR)-532-3p, and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (PIK3CB) were assessed by quantitative real-time polymerase chain reaction or in situ hybridization. Fluorescence in situ hybridization determined the subcellular localization of circFGFR1. Immunohistochemistry was used to detect PIK3CB expression in PDAC tissues. Cell growth was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays. Wound healing, transwell, and flow cytometry assays examined the migration, invasion, and apoptosis. Dual-luciferase and RNA pull-down assay verified the interactions between circFGFR1/PIK3CB and miR-532-3p. In vivo xenograft tumor growth and lung metastasis were assessed in nude mice. RESULTS: Functionally, knockdown of circFGFR1 restrained in vitro PDAC cell growth, migration, invasion, and in vivo xenograft tumor growth and lung metastasis. In addition, circFGFR1 could sponge miR-532-3p to upregulate PIK3CB level. Rescue experiments revealed that the tumor-suppressive effects caused by miR-532-3p mimics could be reversed by circFGFR1 or PIK3CB overexpression. CONCLUSIONS: Our data revealed that circFGFR1 driven the malignant progression of PDAC by targeting miR-532-3p/PIK3CB axis, suggesting that inhibition of circFGFR1 might be considered as a therapeutic target for PDAC.

Application of the Preoperative Assistant System Based on Machine Learning in Hepatocellular Carcinoma Resection.

To conduct better research in hepatocellular carcinoma resection, this paper used 3D machine learning and logistic regression algorithm to study the preoperative assistance of patients undergoing hepatectomy. In this study, the logistic regression model was analyzed to find the influencing factors for the survival and recurrence of patients. The clinical data of 50 HCC patients who underwent extensive hepatectomy (≥4 segments of the liver) admitted to our hospital from June 2020 to December 2020 were selected to calculate the liver volume, simulated surgical resection volume, residual liver volume, surgical margin, etc. The results showed that the simulated liver volume of 50 patients was 845.2 + 285.5 mL, and the actual liver volume of 50 patients was 826.3 ± 268.1 mL, and there was no significant difference between the two groups (t = 0.425; P > 0.05). Compared with the logistic regression model, the machine learning method has a better prediction effect, but the logistic regression model has better interpretability. The analysis of the relationship between the liver tumour and hepatic vessels in practical problems has specific clinical application value for accurately evaluating the volume of liver resection and surgical margin.

miR-188-5p inhibits proliferation, migration, and invasion in gallbladder carcinoma by targeting Wnt2b and Smad2.

Gallbladder carcinoma (GBC) commonly occurs in gastrointestinal malignancy and has the fifth highest mortality rate among gastrointestinal malignancy. Recently, miR-188-5p, a small noncoding RNA, has been implicated in various types of cancer such as nasopharyngeal carcinoma, oral squamous cell carcinoma, liver cancer, and prostate cancer. However, the effect of miR-188-5p on GBC remains unclear. Here, we demonstrated that miR-188-5p was downregulated in GBC tissues, and downregulation of miR-188-5p correlated with larger tumor size, lymph node metastasis, and extensive metastasis. In addition, the overall survival time of patients with higher miR-188-5p expression was significantly longer than that of patients with low-miR-188-5p expression. Moreover, downregulation of miR-188-5p promoted the proliferation, migration, and invasion of GBC cells, while its overexpression inhibited cell invasion and induced cell apoptosis, and arrested GBC growth in vivo. Importantly, miR-188-5p-dependent tumorigenesis was correlated with Wnt/ß-catenin signaling and p-38/JNK signaling. In conclusion, miR-188-5p plays a direct role in GBC tumorigenesis. Our study suggests that miR-188-5p could serve as a novel diagnosis marker and therapeutic target in GBC.

Knockout of LATS1 induces neoplastic phenotype in hepatic oval cells.

BACKGROUND: Primary liver cancer (PLC) is the second leading cause of cancer-related death worldwide. It has been reported that PLC can be originated from malignant transformed adult hepatic progenitor cells. Mammalian large tumor suppressor kinase 1 (LATS1) is one of the core components of the Hippo pathway and it has been implicated in regulating invasion and metastasis of different cancer cell. However, the underlying connections between hepatic progenitor cells and LATS1 in the pathogenesis of PLC are still elusive. METHODS: LATS1 gene knockout (LATS1-KO) hepatic oval cells (HOCs) were constructed by the CRISPR/Cas9 system. Cell viability was evaluated by the CCK-8 assay. Cell migration was measured by scrape assay. Cell invasion was examined by Transwell assay. Cell apoptosis was evaluated by flow cytometry. The expression of LATS1 and Yes-associated protein (YAP) in HOCs was determined by Q-PCR and Western blot analysis. RESULTS: Here, we found that knockout of LATS1 significantly induced the migration and invasion of WB-F344 cells. Knockdown of YAP suppressed the neoplastic phenotype of LATS1-KO WB-F344 cells. Furthermore, overexpression of YAP promoted the migration and invasion of LATS1-KO WB-F344 cells. CONCLUSIONS: In summary, the current study demonstrated that LATS1 is required for inhibiting the neoplastic phenotype of normal hepatic progenitor cell via downregulating YAP.

Transplantation of fetal liver epithelial progenitor cells ameliorates experimental liver fibrosis in mice.

AIM: To investigate the effect of transplanted fetal liver epithelial progenitor (FLEP) cells on liver fibrosis in mice. METHODS: FLEP cells were isolated from embryonal day (ED) 14 BALB/c mice and transplanted into female syngenic BALB/c mice (n = 60). After partial hepatectomy (PH), diethylnitrosamine (DEN) was administered to induce liver fibrosis. Controls received FLEP cells and non-supplemented drinking water, the model group received DEN-spiked water, and the experimental group received FLEP cells and DEN. Mice were killed after 1, 2, and 3 mo, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), and laminin (LN) in serum, and hydroxyproline (Hyp) content in liver were assessed. Alpha-smooth muscle actin (alpha-SMA) of liver was tested by immunohistochemistry. Transplanted male mice FLEP cells were identified by immunocytochemistry for sry (sex determination region for Y chromosome) protein. RESULTS: Serum ALT, AST, HA, and LN were markedly reduced by transplanted FLEP cells. Liver Hyp content and alpha-SMA staining in mice receiving FLEP cells were lower than that of the model group, which was consistent with altered liver pathology. Transplanted cells proliferated and differentiated into hepatocytes and bile duct epithelial cells with 30%-50% repopulation in the liver fibrosis induced by DEN after 3 mo. CONCLUSION: Transplanted FLEP cells proliferate and differentiate into hepatocytes and bile duct epithelial cells with high repopulation capacity in the fiberized liver induced by DEN, which restores liver function and reduces liver fibrosis.