Dataset Information

JWA suppresses proliferation in trastuzumab-resistant breast cancer by downregulating CDK12.

ABSTRACT: Breast cancer is the most common cancer worldwide. JWA is a microtubule-associated protein that has been identified as a tumor suppressor, and its downregulation in tumors is an independent adverse prognostic factor. The objective of this study was to explore the expression, regulation, and mechanism of JWA in trastuzumab-resistant breast cancers. In this study, we found that JWA expression was lower in trastuzumab-resistant breast cancers than that in trastuzumab-sensitive breast cancers. Furthermore, it was confirmed that overexpression of JWA inhibited proliferation and promoted apoptosis in trastuzumab-resistant breast cancers both in vitro and in vivo. In addition, the low expression of JWA in trastuzumab-resistant breast cancers is associated with a poor prognosis. Combining RNA-sequence datasets and next-generation sequencing, it was found that JWA negatively regulated CDK12, and was involved in the G1-to-S transition of the cell cycle. It has been reported that CDK12 drives breast cancer initiation and induces trastuzumab resistance. Taken together, high expression of JWA could inhibit the growth of trastuzumab-resistant breast cancer, and JWA is a potential predictive marker for trastuzumab resistance. In addition, targeted therapy with JWA may be a novel therapeutic strategy to improve the survival rate of trastuzumab-resistant breast cancer.

SUBMITTER: Liang Y

PROVIDER: S-EPMC8536718 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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JWA suppresses proliferation in trastuzumab-resistant breast cancer by downregulating CDK12.

Liang Yan Y Qian Chao C Xie Yinghong Y Huang Xiang X Chen Junjie J Ren Yanlin Y Fu Ziyi Z Li Yongfei Y Zeng Tianyu T Yang Fan F Zhou Jianwei J Li Wei W Yin Yongmei Y Wang Changqing C

Cell death discovery 20211022 1

Breast cancer is the most common cancer worldwide. JWA is a microtubule-associated protein that has been identified as a tumor suppressor, and its downregulation in tumors is an independent adverse prognostic factor. The objective of this study was to explore the expression, regulation, and mechanism of JWA in trastuzumab-resistant breast cancers. In this study, we found that JWA expression was lower in trastuzumab-resistant breast cancers than that in trastuzumab-sensitive breast cancers. Furth ...[more]

PMID: 34686673

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Project description:The Human Epidermal Growth Receptor 2, or the HER2 is one of the highest expressed negative receptor that constitutes approximately 15-20% of malevolent breast cancerous tumors among women. The prevalence of HER2 has untimely and unfavorable consequences on breast cancer, and its underlying carcinomous cell processes, structures, and growth. Trastuzumab (TRZ), a humanized antibody that is rooted in relatively recent foundations, has been found operational in its construction of treatments against HER2-positive breast cancer. This drug is combined with radiotherapy or chemotherapy to deregulate HER2 genes in the body. However, patients who suffer from evolved tumors in advanced stages of cancer exhibit a good amount of tolerance towards singularly used TRZ treatment. Inversely, the factorization of Tumor Testing Fields (TTFields or TTFs) into cancer therapy revives the functions of a TRZ treatment plan, by sensitizing the HER2 genes to the drug. In turn, this facilitates TRZ to continue limiting cancerous cell multiplication and toxicity levels within the treatment. This research evaluates the aspects and effects of this pairing, both in vivo and in vitro through BT474 cells. The TTFields conduct an electromagnetic boundary, which generates sine-wave radiations to manipulate the HER2 gene structure. The methods followed in the research also examines the gene cell cultures and their viability through solutions like Tryptophan blue, or the Crystal violet which may or may not deliver certain testmants to the experiment. The Western Blot Test and the IHC confirm the presence of antibodies and negative receptors in the BT474 cells. These procedures contribute to the formulation of a treatment plan that overcomes the TRZ-resistant nature of the tumor, which is essentially the aim of the research. Thus, the paper substantiates that a healthy combination of TTF's with TRZ can enhance the penetration of TRZ after inducing apoptosis due to TTFields therapy. The success of a TTField in undertaking this pursuit makes room for more utilization of it in future cancerous treatment ventures.

Dataset Information

JWA suppresses proliferation in trastuzumab-resistant breast cancer by downregulating CDK12.

Publications

JWA suppresses proliferation in trastuzumab-resistant breast cancer by downregulating CDK12.

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