Retraction: Inhibition of ClC-5 suppresses proliferation and induces apoptosis in cholangiocarcinoma cells through the Wnt/ß-catenin signaling pathway.

[Retraction to: BMB Rep. 2022 June 30; 55(6): 299-304.] Retraction: "Inhibition of ClC-5 suppresses proliferation and induces apoptosis in cholangiocarcinoma cells through the Wnt/ß-catenin signaling pathway," by Zhe Shi, Liyuan Zhou, Yan Zhou, Xiaoyan Jia, Xiangjun Yu, Xiaohong An and Yanzhen Han, BMB Rep. 2022; 55(6) 299-304: The above article, published online on 30 June 2022 in BMB Reports https://doi.org/10.5483/ BMBRep.2022.55.6.044), has been retracted by agreement between the authors and the journal's Editor in Chief. The authors unable to replicate certain results presented in the article and have therefore made the difficult decision to withdraw it. Editorial Board, BMB Reports.

Di-(2-ethylhexyl) phthalate aggravates fine particulate matter-induced asthma in weanling mice due to T follicular helper cell-dependent response.

Environmental pollutants fine particulate matter and di-(2-ethylhexyl) phthalate (DEHP) are believed to be the risk factors for childhood asthma. Allergic asthma is basically an immediate hypersensitivity mediated by IgE, the product of humoral immune response. T follicular helper cells (Tfh) have been newly identified as the crucial T helper cells for supporting B cells to produce immunoglobulins in humoral immunity. Tfh cells are therefore potentially to serve as the diagnostic marker and therapeutic target of immune diseases. In this study, we examined the joint effects of fine particulate matter and DEHP on the initiation and progression of asthma and explored the fundamental role of Tfh cells during the process. Weanling C57BL/6 mice (both sexes) were concurrently exposed to DEHP (intragastric administration at 300 µg/kg) and fine atmospheric particulate matter (mean particle diameter < 4 µm, PM4) (oropharyngeal instillation at 2 mg/kg) once every three days for 30 days (10 times). We found that DEHP displayed adjuvant effects to potentiate PM4 allergen-induced expansion of Tfh and plasma cells, production of serum IgE and IgG1, and occurrence of airway hyper-responsiveness and inflammation. Then PM4 and DEHP co-exposure was performed to Cd4 knock-out mice reconstituted with normal wild-type adoptive Tfh cells or non-Tfh cells. The results of immune adoptive transfusion indicated that the joint immunotoxic effects of PM4 and DEHP were dependent on Tfh cells. We further proved that DEHP could adjuvantly boost PM4-induced expression of BCL-6 and c-MAF and secretion of IL-13 and IL-4 in Tfh cells. In conclusion, these data suggest that DEHP metabolites act in an adjuvant-like manner to aggravate PM4 allergen-induced asthma based on anaphylactic IgE response, resulting from excessive IL-13 and IL-4 synthesized by abnormally differentiated Tfh cells.

Inhibition of ClC-5 suppresses proliferation and induces apoptosis in cholangiocarcinoma cells through the Wnt/ß-catenin signaling pathway.

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/ß-catenin signaling activity and further activate the mitochondria apoptotic pathway in CCA cells. Furthermore, rescuing Wnt/ß-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/ß-catenin pathway, which in turn activates the mitochondrial apoptotic pathway. [BMB Reports 2022; 55(6): 299-304].

Blockade of chloride channel-3 enhances cisplatin sensitivity of cholangiocarcinoma cells though inhibiting autophagy.

Chemotherapy is one of the most important strategies in the treatment of cancer; however, chemoresistance 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 tumours, while its role in the chemotherapy of cholangiocarcinoma (CCA) is still poorly understood. Herein, we observed that ClC-3 was highly expressed in CCA chemoresistant 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.

MicroRNA-325-3p inhibits cell proliferation and induces apoptosis in hepatitis B virus-related hepatocellular carcinoma by down-regulation of aquaporin 5.

BACKGROUND: Hepatitis 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. METHODS: AQP5 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. RESULTS: In 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. CONCLUSIONS: Our 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.