To the best of our knowledge, we are the first to report this regulatory mechanism of MIR100HG in TNBC. The ERK/MAPK signalling pathway, the most well-documented MAPK signalling pathway, is closely involved in cell proliferation and differentiation, angiogenesis and tumour metastasis , and it also plays a crucial role in the cell signal N-Acetyl-D-mannosamine transduction network . pathway were assessed by western blot analysis. Bioinformatics and luciferase assay were performed to predict and validate the conversation between MIR100HG and miR-5590-3p as well as OTX1 and miR-5590-3p. RNA immunoprecipitation (RIP) was used to detect the conversation between MIR100HG and miR-5590-3p. Subcutaneous tumour growth was observed in nude mice. Immunohistochemistry (IHC) analysis was used to assess OTX1 expression in tumour tissues. Results MIR100HG expression was upregulated, whereas that of miR-5590-3p was downregulated in TNBC. MIR100HG was shown to directly interact with miR-5590-3p. Furthermore, MIR100HG knockdown could promote TNBC cell apoptosis and cell cycle arrest in G0/G1 phase while inhibiting migration, invasion and proliferation. Furthermore, miR-5590-3p inhibition showed the opposite results and could reverse the effect of MIR100HG knockdown in TNBC cells. MiR-5590-3p downregulated the ERK/MAPK signalling pathway, suppressed the migration, invasion and proliferation of TNBC cells and promoted their apoptosis and cell cycle arrest in G0/G1 phase by targeting OTX1. In addition, MIR100HG knockdown inhibited OTX1 expression by upregulating miR-5590-3p in vivo, thereby inhibiting tumour growth. Conclusions MIR100HG promotes the progression of TNBC by sponging miR-5590-3p, thereby upregulating OTX1, suggesting a new potential treatment target for TNBC. strong class=”kwd-title” Keywords: TNBC, MIR100HG, miR-5590-3p, OTX1 Background As the most common malignancy in women, breast cancer has become the dominant cause of cancer-associated death and is divided into a variety of molecular subtypes, among which TNBC is the most aggressive and has a high risk of recurrence [1, 2]. Due to the absence N-Acetyl-D-mannosamine of progesterone receptor (PR), oestrogen receptor (ER) and epidermal growth factor receptor 2 (HER-2) being characteristics of TNBC, effective targeted therapies remain lacking for this disease , with the 5-year survival rate of patients being only 60% . Thus, it is of great importance to elucidate the molecular mechanisms associated with the development N-Acetyl-D-mannosamine of TNBC, which will pave the way to develop novel effective therapies for this malignancy. LncRNAs are a class of noncoding RNAs longer than 200 nucleotides without coding potential that are involved in the regulation of various diseases, including cancer [5, 6]. Recently, lncRNAs have been recognized to play important roles in the genesis and progression of TNBC [7C9]. However, the underlying molecular mechanisms associated with this process require further elucidation. Some lncRNAs are referred to as miRNA-host gene lncRNAs (lnc-miRHGs), as they harbour miRNAs within their sequences . However, only a few studies to date have focused on the miRNA-independent roles of lnc-miRHGs that are independent of the miRNAs from which they are processed. LncRNA MIR100HG takes part in cancer progression in both miRNA-independent and -dependent manners. For example, it can promote the migration and proliferation of laryngeal squamous cell carcinoma cells  and can also N-Acetyl-D-mannosamine function as oncogene in acute megakaryoblastic leukaemia . Recently, the regulatory role of MIR100HG in promoting TNBC cell proliferation has also been reported . However, research around the molecular mechanism of MIR100HG in TNBC is currently limited. Thus, additional efforts should be made to unravel its regulatory mechanism in greater depth. MicroRNAs (miRNAs) are approximately 20-22nt long endogenous RNAs that are involved in regulating multiple physiological biological processes, such as tumourigenesis and metastasis . MiRNAs are also involved in the progression of TNBC . Recent studies have shown that miR-5590-3p is also involved in the regulation of cancer, being able to inhibit diffuse large B cell lymphoma progression and immune evasion . In addition, it can also regulate tumour growth and metastasis in hepatocellular carcinoma through the Wnt/-catenin pathway . In particular, miR-5590-3p is downregulated in TNBC . However, the relationship between miR-5590-3p and MIR100HG has not been reported. Thus, it is of great importance to investigate the regulatory mechanism between miR-5590-3p on MIR100HG in TNBC progression. In the present study, we assessed biological function of MIR100HG in TNBC and present evidence that it promotes tumourigenesis in TNBC through the miR-5590-3p/OTX1 axis. Collectively, the results of the present study elucidated the molecular Rabbit Polyclonal to GPR142 mechanism of MIR100HG in regulating TNBC progression and explored the potential of MIR100HG inhibition as an anti-TNBC therapeutic target. Methods Patient tissues The present study was approved by the Ethics Committee of Xiangya Hospital of Central South University. The study followed the tenets of the Declaration of Helsinki, and written informed consent was obtained from all patients. Twenty paired TNBC tissue samples and adjacent normal tissue samples.