MUC16 affects the biological functions of ovarian cancer cells and induces an antitumor immune response by activating dendritic cells
Authors: Qi Lu
Shuzhen Wang
Yan Zhai
Guangming Cao
Zhenyu Zhang
Tong Lou
Journal: Annals of Translational Medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: Mucin16 (MUC16); Ovarian cancer; cytotoxic T lymphocyte (CTL); dendritic cells (DCs) vaccine.
Affiliations: Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Abstract:  Background: Ovarian cancer is the 5th most common lethal gynecological malignancy with a 5-year survival rate of about 47% and a localized stage diagnosis of 15%, leading to about 125,000 global deaths each year. Therefore, it is urgent to explore novel and effective strategies for radical cure. Methods: Short hairpin RNA targeting the Mucin16 (MUC16) gene was used to establish MUC16 knockdown in ovarian cancer cells. RT-PCR was performed to quantify the expression of MUC16 mRNA, and western blotting was performed to detect the expression of MUC16 and epithelial-mesenchymal transition-related proteins. Cell counting kit 8 (CCK8) wound healing and transwell assays were performed to assess cell proliferation and cell invasion. Flow cytometry was used to detect CD80-, CD83-, and CD86-expressing dendritic cells (DCs) and cytotoxic T lymphocytes (CTLs) activated by MUC16-pulsed DCs. Results: In this study, we identified MUC16 as a novel target antigen for immunotherapy against ovarian cancer, which was significantly up regulated in ovarian cancer cells and high-grade ovarian serous adenocarcinoma tissues. MUC16 knockdown in Ovcar3 cells using short hairpin RNA targeting the MUC16 gene suppressed the proliferation of migration, invasion, epithelial-mesenchymal transition (EMT), and PI3K/Akt signaling pathway in Ovcar3 cells markedly. MUC16 significantly up-regulated CD80, CD83, and CD86 (mature makers) expression in DCs and T-cell transformation into CD8+ T-cells detected by Flow cytometry. Conclusions: For malignant ovarian cancer, MUC16 overexpression promoted cell proliferation, migration, and invasion via the PI3K/AKT signaling pathway. MUC16 pulsing mediated DC maturation and activated CTL response in vitro. Our study offers promising DC-based immunotherapy of considerable clinical value for patients with ovarian cancer. 

Retracted: No

PubPeer comments:
 Identified by another reader. *** ![file] , 
 First published: 18 December 2012 https: doi.org 10.1111 bph.12032 In Yadav etu2009al., (2012), errors appeared in Figureu20092E and Figureu20095D. It was found that beta actin, the loading control in Figureu20092E, was inadvertently duplicated from Figureu20093A during figure assembly. An inadvertent error was also noted in Figureu20095D with PARP bands. Thus, experiments representing these figures were repeated. The correct versions of these figures, are now reproduced below. The authors would like to apologize for these errors. ![file] ![file] The editors of BJP believe that there should be a full explanation of any published corrigendum. After a full and thorough review of all the issues, the editors accept that errors in the figures were compiling errors by the authors. It is important to note that the correction of the errors does not change our judgement that this paper is suitable for publication nor does it alter the conclusions in the manuscript. ,