LncRNA MBNL1-AS1 Represses Proliferation and Cancer Stem-Like Properties of Breast Cancer through MBNL1-AS1/ZFP36/CENPA Axis

Abstract

Background. Emerging studies have revealed long noncoding RNAs (lncRNAs) were key regulators of cancer progression. In this research, the expression and roles of MBNL1-AS1 were explored in breast cancer (BC). Methods. In this study, the MBNL1-AS1 expression in breast cancer tissue, as well as in cell line, was studied by qRT-PCR assays. The effects of MBNL1-AS1 on proliferation and stemness were evaluated by MTT assays, colony formation assays, orthotopic breast tumor mice models, extreme limiting dilution analysis (ELDA), fluorescence in situ hybridization (FISH), flow cytometry assays, and sphere formation assays. Flexmap 3D assays were performed to show that MBNL1-AS1 downregulated the centromere protein A (CENPA) secretion in BC cells. Western blot, RNA pull-down assays, RNA immunoprecipitation (RIP) assays, and FISH were conducted to detect the mechanism. Results. The results showed that the expression levels of MBNL1-AS1 were downregulated in breast cancer tissues and cell lines. In vitro and in vivo studies demonstrated that overexpression of MBNL1-AS1 markedly inhibited BC cells proliferation and stemness. RNA pull-down assay, RIP assay, western blot assay, and qRT-PCR assay showed that MBNL1-AS1 downregulated CENPA mRNA via directly interacting with Zinc Finger Protein 36 (ZFP36) and subsequently decreased the stability of CENPA mRNA. Restoration assays also confirmed that MBNL1-AS1 suppressed the CENPA-mediated proliferation and stemness in breast cancer cells. Conclusions. The new mechanism of how MBNL1-AS1 regulates BC phenotype is elucidated, and the MBNL1-AS1/ZFP36/CENPA axis may be served as a therapeutic target for BC patients.

CENPA knockdown restrains cell progression and tumor growth in breast cancer by reducing PLA2R1 promoter methylation and modulating PLA2R1/HHEX axis

“…An integrated expression profiling analysis identified that high CENPA level in triple-negative breast cancer was correlated with poor prognosis, thereby suggesting its potential clinical therapeutic applications [34]. In addition, a recent study revealed the upstream regulatory genes of CENPA, which suggested that lncRNA MBNL1-AS1/ MBNL1-AS1/ZFP36 axis suppressed proliferation and cancer stem-like properties of breast cancer cells through reducing CENPA mRNA stability [35]. Given the momentous roles of CENPA in breast cancer, our study investigated the accurate functions and downstream pathways of CENPA in breast cancer progression.…”

Exosomal miRNA-223-3p derived from tumor associated macrophages promotes pulmonary metastasis of breast cancer 4T1 cells

“…More mechanisms are still under exploration. Other genes predicted to be the targets of miR-223-3p from database have also been found to have some anti-tumor effects, such as FAT1, whose significantly decrease has been reported to be associated with poor prognosis and invasiveness in invasive ductal carcinoma [35] ; MBNL1 is demonstrated to be significantly downregulated in breast and gastric cancers in several studies, and MBNL1 can interact directly with ZFP36 to downregulate CENPA, thereby inhibiting the proliferation and stemness of breast cancer cells [ 36 , 37 ]. CBFB, together with its binding partner RUNX1, regulates multiple signaling pathways, and breast cancer cells may evade both translational and transcriptional surveillance simultaneously caused by CBFB downregulation [38] .…”

BPIFB1 promotes metastasis of hormone receptor‐positive breast cancer via inducing macrophage M2‐like polarization

“…Animal studies were permitted by the Joint Ethics Committee of the Harbin Medical University Health Authority (Harbin, China). 37 T47D cell lines expressing luciferase were used for in vivo experiments. Female NOD/SCID mice (Vital Rivers, China) were housed in a specific pathogen‐free barrier facility with a 12‐h light/12‐h dark cycle.…”

“…Animal studies were permitted by the Joint Ethics Committee of the Harbin Medical University Health Authority (Harbin, China) 37. T47D cell lines expressing luciferase were used for in vivo experiments.…”