STARD13-correlated ceRNA network-directed inhibition on YAP/TAZ activity suppresses stemness of breast cancer via co-regulating Hippo and Rho-GTPase/F-actin signaling

• Published in: Journal of hematology and oncology Vol. 11; no. 1; pp. 72 - 18
• Main Authors: Zheng, Lufeng, Xiang, Chenxi, Li, Xiaoman, Guo, Qianqian, Gao, Lanlan, Ni, Haiwei, Xia, Yufeng, Xi, Tao
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.05.2018; BioMed Central; BMC
• Subjects: 3' Untranslated regions; Actin; Actins - metabolism; Adaptor Proteins, Signal Transducing - metabolism; Analysis; Binding sites; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer therapies; Care and treatment; Cell Line, Tumor; Cellular signal transduction; Chemoresistance; Chemotherapy; Development and progression; Gene expression; Genetic aspects; Genomes; GTP Phosphohydrolases - metabolism; GTPase-Activating Proteins - metabolism; GTPase-Activating Proteins - pharmacology; Guanine nucleotide-binding protein; Guanosine triphosphatases; Hematology; Humans; Intracellular Signaling Peptides and Proteins - metabolism; Kinases; Metastasis; MicroRNAs; Neoplastic Stem Cells - chemistry; Oncology; Phosphoproteins - metabolism; Physiological aspects; Protein-Serine-Threonine Kinases - metabolism; Ribonucleic acid; RNA; RNA - metabolism; Signal transduction; Signal Transduction - drug effects; STARD13 ceRNA YAP/TAZ Hippo F-actin CSC breast cancer; Stem cells; Trans-Activators; Transcription; Transcription Factors - metabolism; Tumor Suppressor Proteins - metabolism; Tumor Suppressor Proteins - pharmacology; Tumors; Yes-associated protein; China; United States > US; STARD13 ceRNA YAP/TAZ Hippo F-actin CSC breast cancer
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-018-0613-5

Targeting cancer stem cells is critical for suppressing cancer progression and recurrence. Finding novel markers or related pathways could help eradicate or diagnose cancer in clinic. By constructing STARD13-correlated ceRNA 3'UTR stable overexpression or knockdown breast cancer cells, we aimed to explore the effects of STARD13-correlated ceRNA network on breast cancer stemness in vitro and in vivo. Further RNA-sequencing was used to analyze transcriptome change in combination with functional studies on candidate signaling. Clinical samples obtained from The Cancer Genome Atlas data were used to validate the correlation between STARD13 and related pathways. Finally, in vitro and in vivo experiments were used to examine the effects of STARD13-correlated ceRNA network on chemotherapy sensitivity/resistance. Here, we revealed that this ceRNA network inhibited stemness of breast cancer. Mechanistically, we found that activation of STARD13-correlated ceRNA network was negatively correlated with YAP/TAZ activity in breast cancer. Specifically, this ceRNA network attenuated YAP/TAZ nuclear accumulation and transcriptional activity via collectively modulating Hippo and Rho-GTPase/F-actin signaling. Finally, we demonstrated that YAP/TAZ transcriptional activity regulated by this ceRNA network was involved in chemoresistance. Our results uncover a novel mechanism of YAP/TAZ activation in breast cancer and propose the possibility to drive STARD13-correlated ceRNA network to inhibit breast cancer stem cell traits.