BackgroundHepatitis B virus (HBV) infection is acknowledged as the main cause of hepatocellular carcinoma (HCC). Moreover, previous studies have revealed that microRNAs (miRNAs) widely participate in regulation of various cellular processes, such as viral replication. Hence, the purpose of this study was to investigate the roles of aquaporin 5 (AQP5) and miR-325-3p in the proliferation and apoptosis of HBV-related HCC cells.MethodsAQP5 and miR-325-3p expression in both normal and HBV-HCC tissues or cells (both Huh7–1.3 and HepG2.2.15) was detected using qRT-PCR. AQP5 expression was knocked down in HBV-related Huh7–1.3 and HepG2.2.15 cells using small interfering RNA (siRNA) technology. Down-regulation was confirmed using real-time PCR and Western blot analysis. Effects of AQP5 down-regulation on the proliferation and apoptosis were assessed. Dual luciferase reporter gene assay, Western blot and qRT-PCR were employed to evaluate the effect of miR-325-3p on the luciferase activity and expression of AQP5. Moreover, miR-325-3p mimic-induced changes in cellular proliferation and apoptosis were detected through CCK-8 assay, BrdU assay, flow cytometry analysis and ELISA.ResultsIn this study, the expression of AQP5 was up-regulated in human HBV-HCC tissue, Huh7–1.3 and HepG2.2.15 cells. Knockdown of AQP5 significantly inhibited the proliferation and promoted apoptosis of HBV-HCC cells. Next, miR-325-3p was obviously down-regulated in HBV-HCC. In concordance with this, MiR-325-3p directly targeted AQP5, and reduced both mRNA and protein levels of AQP5, which promoted cell proliferation and suppressed cell apoptosis in HCC cells. Overexpression of miR-325-3p dramatically inhibited cell proliferation and induced cell apoptosis.ConclusionsOur findings clearly demonstrated that introduction of miR-325-3p inhibited proliferation and induced apoptosis of Huh7–1.3 and HepG2.2.15 cells by directly decreasing AQP5 expression, and that silencing AQP5 expression was essential for the pro-apoptotic effect of miR-325-3p overexpression on Huh7–1.3 and HepG2.2.15 cells. It is beneficial to gain insight into the mechanism of HBV infection and pathophysiology of HBV-related HCC.

The identification of specific drug targets guides the development of precise cancer treatments. Compared with oncogenes, tumor suppressor genes have been poorly studied in the treatment of breast cancer. We integrate the microRNA expression array from GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) databases in clinical breast cancer tissues, and find that miR-27a is significantly upregulated and correlated with poor survival outcome and tumor progression. Transmembrane protein 170B (TMEM170B), a new functional target of miR-27a, is identified via target prediction and experimental validation, suppressing breast cancer proliferation, metastasis, and tumorigenesis. Furthermore, TMEM170B overexpression promotes cytoplasmic β-catenin phosphorylation, resulting in the inhibition of β-catenin stabilization, reduction of nuclear β-catenin levels and downstream targets expression. Clinically, TMEM170B or β-catenin expression is significantly correlated with overall survival ratio in breast cancer patients. Thus, these results highlight TMEM170B as a novel tumor suppressor target in association with the β-catenin pathway, which may provide a new therapeutic approach for human breast cancer therapy.

Increasing evidence has confirmed that the dysregulation of microRNAs (miRNAs) contributes to the proliferation and invasion of human cancers. Previous studies have shown that the dysregulation of miR-124 is in numerous cancers. However, the roles of miR-124 in human osteosarcoma (OS) have not been well clarified. Therefore, this study was to investigate the biological functions and molecular mechanisms of miR-124 in OS cell lines, discussing whether it could be a therapeutic biomarker of OS in the future. In this study, our results demonstrated that miR-124 was down-regulated in OS cell lines and tissues. Furthermore, the low level of miR-124 was associated with increased expression of Sphingosine kinase 1 (SPHK1) in OS cells and tissues. Up-regulation of miR-124 significantly inhibited cell proliferation, invasion, and MMP-2 and -9 expressions of OS cells. Bioinformatics analysis predicted that the SPHK1 was a potential target of miR-124. Further study by luciferase reporter assay demonstrated that miR-124 could directly target SPHK1. Overexpression of SPHK1 in OS cells transfected with miR-124 mimic partially reversed the inhibitory of miR-124. In conclusion, miR-124 inhibited cell proliferation and invasion in OS cells by downregulation of SPHK1, and that downregulation of SPHK1 was essential for the miR-124-inhibited cell invasion and in OS cells.

Lycium barbarum polysaccharide (LBP) is the main active component of Lycium barbarum and has many beneficial effects, including neuroprotection, antiaging, and antioxidation. This study mainly explores the immunomodulatory effect of Lycium barbarum polysaccharides against liver fibrosis based on the intelligent medical Internet of Things. This measure emphasizes that the current effective methods and methods for the treatment of liver cancer are mainly combined treatments of Western medicine and Chinese medicine. These treatments have a certain effect in preventing liver cancer, reducing recurrence, and reducing side effects. Among them, chemotherapy has unique advantages in improving the quality of life and prolonging survival. With the development of medical science and technology, the clinical efficacy and efficacy of traditional Chinese medicine in the treatment of liver cancer are constantly improving. The mechanism is also studied from many aspects. The treatment time of LBPs on fibrotic hepatocytes was set to 24 h. Take liver fiber cells in logarithmic growth phase and incubate them at 37°C for 24 h. The whole process uses a temperature sensor for intelligent temperature control. In the experiment, groups of LBPs with different concentrations and different molecular weight ranges were set up and each group had 6 multiple holes. The original medium was aspirated and replaced with a medium containing different concentrations of LBPs (12.5, 25, 50, 100, and 200 μg/mL) and cultured for 24 h. Based on the previous research, this study used in vitro cell experiments, microscopic observation, and MTT method to verify whether Lycium barbarum polysaccharides inhibit the proliferation of human liver cancer cells in vitro and whether they cooperate with the chemotherapy drug fluorouracil to play a tumor-killing effect. Animal experiments, using ELISA, HE staining, and other methods, explore the molecular and immunological mechanisms of LBP’s antiliver cancer effect from the perspective of Th/Th2 differentiation balance and DC function, in order to provide experimental evidence for Chinese medicine polysaccharides in cancer immunotherapy and application. At different LBP concentrations (0 μmol/L, 5 μmol/L, 10 μmol/L, and 15 μmol/L), the inhibition rates were 0.80%, 20.06%, 35.44%, and 55.39%, respectively. This study provides a new method for large-scale expansion of hepatocytes in vitro, laying a stronger foundation for biological treatment of liver fibrosis.

Chemotherapy is one of the most important strategies in the treatment of cancer, however, chemo-resistance restricts the effect of chemotherapy. Growing reports suggest that chloride channel-3 (ClC-3) is involved in regulating the sensitivity of multiple chemotherapeutic agents in the chemotherapy of various tumors, while its role in the chemotherapy of cholangiocarcinoma (CCA) is still poorly understood. Herein, we observed that ClC-3 was highly expressed in CCA chemo-resistant tissues and CCA cisplatin-resistant cells QBC939/DDP, and, the sensitivities of QBC939 and QBC939/DDP cells to cisplatin were all increased after inhibition of ClC-3. Further mechanism exploration revealed that ClC-3 knockdown reduced the level of autophagy. Furthermore, in both QBC939 and QBC939/DDP cells, the autophagy agonist rapamycin eliminated the increased cisplatin sensitivity of ClC-3 knockdown without affecting ClC-3 expression. Collectively, all the findings demonstrate that ClC-3 knockdown increases cisplatin-induced cell death in CCA cells though inhibiting autophagy, regardless of the occurrence of cisplatin resistance. In addition, our results also suggest that targeted inhibition of ClC-3 may be a potential strategy for chemosensitization in CCA chemotherapy.

Chloride channel-5 (ClC-5), an important branch of the ClC family, is involved in the regulation of the proliferation and cell-fate of a variety of cells, including tumor cells. However, its function in cholangiocarcinoma (CCA) cells remains enigmatic. Here, we discovered that ClC-5 was up-regulated in CCA tissues and CCA cell lines, while ClC-5 silencing inhibited CCA cell proliferation and induced apoptosis. Further mechanism studies revealed that ClC-5 inhibition could inhibit Wnt/β-catenin signaling activity and further activate the mitochondria apoptotic pathway in CCA cells. Furthermore, rescuing Wnt/β-catenin signaling activation eliminated the anti-tumor function of ClC-5 knockdown. Together, our research findings illustrated that ClC-5 inhibition plays an anti-tumor role in CCA cells via inhibiting the activity of the Wnt/β-catenin pathway, which in turn activates the mitochondrial apoptotic pathway. [BMB Reports 2022; 55(6): 299-304]

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