<p>ANLN Directly Interacts with RhoA to Promote Doxorubicin Resistance in Breast Cancer Cells</p>

Abstract

Background: Chemotherapy resistance is the leading cause of cancer treatment failure. This research was conducted to explore a potential link between actin-binding protein anillin (ANLN) and doxorubicin resistance in breast cancer. Materials and Methods: We compared ANLN expression and 50% inhibition concentration (IC50) of doxorubicin in human breast cancer cells (MDA-MB-231) and human breast cancer cells with doxorubicin resistance (MDA-MB-231/ADM). Co-immunoprecipitation was used to investigate the interaction between ANLN and RhoA. The cell viability, apoptosis, gene and protein expression were estimated by MTT, flow cytometry, quantitative real-time PCR and western blot. Results: The doxorubicin resistance in MDA-MB-231/ADM cells (IC50 = 19.40 ± 1.16 μg/ mL) was significantly higher than that in MDA-MB-231 cells (IC50 = 1.65 ± 0.23 μg/mL). ANLN was up-regulated in MDA-MB-231/ADM cells compared to MDA-MB-231 cells. Furthermore, ANLN overexpression promoted cell viability and inhibited apoptosis of MDA-MB-231 cells. The gene and protein expression of multidrug resistance (MDR1) and cancer resistance protein (BCRP) were enhanced by ANLN overexpression in MDA-MB-231 cells. ANLN silencing suppressed cell viability and the expression of MDR1 and BCRP and facilitated apoptosis in MDA-MB-231/ADM cells. Moreover, ANLN promoted RhoA activation by interacting with RhoA. ANLN up-regulation enhanced cell viability and the expression of MDR1 and BCRP and decreased apoptosis of MDA-MB-231 cells. The influence conferred by ANLN overexpression was effectively abolished by C3 transferase. Conclusion: This work revealed that ANLN promoted doxorubicin resistance in breast cancer cells by activating RhoA. Thus, our study suggests a novel target for breast cancer treatment.

Integrated Chromatin Accessibility and Transcriptome Landscapes of Doxorubicin-Resistant Breast Cancer Cells

“…Despite a few molecular mechanisms involved in the process of doxorubicin resistance in cancer have been reported (Huang et al, 2018;Lovitt et al, 2018;Stefanski et al, 2019;Jin et al, 2020;Wang et al, 2020;Mirzaei et al, 2021;Yang et al, 2021), drug resistance is almost inevitable in advanced breast cancer patients, which remains a major unresolved issue in the treatment of cancer patients. An increasing number of studies have revealed that the alteration in chromatin accessibility plays a critical role in acquired resistance against cancer drugs (Jing et al, 2018;Zhang et al, 2020), but we still lack precise knowledge of how accessible chromatin state define transcriptional regulatory networks and which are the regulatory elements involved in doxorubicin resistance in breast cancer cells.…”

A Four-Gene Prognostic Signature Based on the TEAD4 Differential Expression Predicts Overall Survival and Immune Microenvironment Estimation in Lung Adenocarcinoma

“…In addition, similar to TEAD4 , three of these genes ( ANLN , KRT6A , and RHOV ) were associated with poor outcomes in LUAD, which were all recognized as oncogenic genes. For instance, ANLN is a well-known oncogene that promotes carcinogenesis and therapeutic resistance in multiple types of cancers, such as LUAD ( Long et al, 2018 ; Xu et al, 2019 ; Deng et al, 2021 ), oral cancer ( Wang B et al, 2021 ), colorectal cancer ( Liu et al, 2022 ), breast cancer ( Wang et al, 2020 ; Maryam and Chin, 2021 ), pancreatic cancer ( Wang et al, 2019 ), and head and neck squamous cell carcinoma ( Guo et al, 2021 ). RHOV has been widely studied to promote LUAD cell growth, metastasis, and therapeutic resistance ( Chen H et al, 2021 ; Zhang et al, 2021 ).…”

Alternative splicing of ANLN synergistically contribute to the progression of head-neck squamous cell carcinoma

“…For instance, it was reported that ANLN promoted pancreatic cancer progression by regulating EZH2/miR-218-5p/LASP1 signaling axis 15 . ANLN promoted doxorubicin resistance in breast cancer cells by activating RhoA 16 . ANLN played a critical role in human lung carcinogenesis through the activation of RHOA and by involvement in the phosphoinositide 3-kinase/AKT pathway 17 .…”