MiR‐145‐targeted HBXIP modulates human breast cancer cell proliferation

Abstract

BackgroundMiR‐145 has been identified as a tumor suppressive microRNA in multiple cancers. In this current investigation, we searched for new direct targets of miR‐145 and evaluated their effect on breast cancer development.MethodsTargetscan was used to predict the target genes of miR‐145. The targeting of miR‐145 on oncogenic HBXIP was verified by luciferase reporter gene analysis. The effect of miR‐145 on the level of messenger RNA and protein of HBXIP was evaluated by quantitative real‐time PCR and immunoblotting. Correlations between miR‐145 and HBXIP, as well as miR‐145 expression, were analyzed in 30 paired breast cancer and noncancerous tissues by quantitative real‐time PCR. Methyl thiazol tetrazolium and colony formation assays were applied to determine the cell proliferation ability.Results HBXIP was identified as a novel target gene of miR‐145 in breast cancer. MiR‐145 was found to dose‐dependently decrease messenger RNA and protein expression of HBXIP in breast cancer MCF‐7 cells. Notably, miR‐145 expression was negatively related to HBXIP expression and was obviously reduced in breast cancer samples. Finally, miR‐145 suppressed cell proliferation while its inhibitor, anti‐miR‐145, accelerated cell proliferation. Interestingly, silencing of HBXIP reversed the acceleration of cell proliferation induced by anti‐miR‐145 in breast cancer.ConclusionOncogenic HBXIP is a new direct target of tumor suppressive miR‐145. Our findings reveal that miR‐145‐targeting HBXIP could be a potential therapeutic target in breast cancer.

RETRACTED ARTICLE: Silencing hsa_circ_PVT1 (circPVT1) suppresses the growth and metastasis of glioblastoma multiforme cells by up-regulation of miR-199a-5p

“…Up to now, miRNAs have been revealed that they are involved in a large amount of biological processes, including tumour formation and inflammatory responses in many human diseases [25][26][27]. It is well known that miR-199a-5p has been studied to take part in the progress of cancer [28].…”

<p>MiR-145 inhibits EGF-induced epithelial-to-mesenchymal transition via targeting Smad2 in human glioblastoma</p>

“…To date, miRNAs have been reported to be implicated into some biological processes, including tumorigenesis and inflammatory response in numerous human diseases 15–17. As known to all, miR-145 has been reported to exert different effects on the development and progression of cancers.…”

“…MiRNAs have been demonstrated to be involved in various human diseases, and play important roles in cellular differentiation, proliferation, metastasis and EMT 12. Notably, aberrant miR-145 expression was also reported to be implicated in cancer progression by regulating target genes 13–15. Using bioinformatics analysis, we found that Smad2 was also a potential candidate target of miR-145.…”

Potential miRNAs for miRNA-Based Therapeutics in Breast Cancer

“…Götte et al, 2010 also demonstrated that miR-145 modulates the actin cytoskeleton remodeling and homogenizes cortical actin distribution, nuclear rotation, and migration via the direct interaction with 3′UTR of JAM-A and fascin in MDA-MB-231 cells [ 154 ]. In a similar context, the expression of SMAD3 [ 148 ], DR5 [ 148 ], BRCA2 [ 148 ], HBXIP [ 155 ] and RTKN [ 156 ] directly silenced by miR-145 inhibits tumor metastasis. Angiogenesis is one of the hallmarks of epithelial–mesenchymal transition (EMT).…”