LncRNA HIF1A-AS2 promotes triple-negative breast cancer progression and paclitaxel resistance via MRPS23 protein.

Dysregulation of lncRNAs is a critical factor in the migration and invasion of tumors. Here our study reveals that lncRNA HIF1A-AS2 is highly expressed in breast cancer tissues and various TNBC cell lines. Moreover, we present compelling evidence supporting the role of HIF1A-AS2 in promoting TNBC cell proliferation, metastasis, invasion, and resistance to paclitaxel treatment. Additionally, our transcriptome sequencing analysis identifies MRPS23 as a potential downstream target protein regulated by HIF1A-AS2 and knockdown of HIF1A-AS2 leads to decreased expression of MRPS23 in TNBC cells. Moreover, MRPS23 exhibits similar effects on enhancing cell proliferation, metastasis, invasion, and paclitaxel resistance in TNBC cells. Furthermore, downregulating HIF1A-AS2 suppresses the enhanced functionality observed in TNBC cells due to upregulated MRPS23 expression. These findings suggest that modulation of MRPS23 protein expression by HIF1A-AS2 may influence cellular processes and paclitaxel sensitivity in TNBC cells.

Suppression of migration and invasion by taraxerol in the triple-negative breast cancer cell line MDA-MB-231 via the ERK/Slug axis.

As one of the triterpene extracts of Taraxacum, a traditional Chinese plant, taraxerol (TRX) exhibits antitumor activity. In this study, we evaluated the effects of TRX on the migration and invasion of MDA-MB-231 cells, analyzed the molecular mechanism through network pharmacology and molecular docking, and finally verified it by in vitro experiments. The results showed that TRX could inhibit the migration and invasion of MDA-MB-231 cells in a time- and concentration-dependent manner, while MAPK3 was the most promising target and could stably combine with TRX. In addition, the relative protein expression levels were detected by Western blot, and we observed that TRX could inhibit the migration and invasion of MDA-MB-231 cells via the ERK/Slug axis. Moreover, an ERK activator (tert-butylhydroquinone, tBHQ) partially reversed the suppressive effect of TRX on MDA-MB-231 cells. In conclusion, TRX inhibited the migration and invasion of MDA-MB-231 cells via the ERK/Slug axis.

Therapeutic potential of anti-miR29a in breast cancer patients with type 2 diabetes: an in vitro and xenograft mouse-model study.

Background: MicroRNAs (miRNAs) acting as tumour suppressors or oncogenes, known as oncomiRs, are a promising new focus in targeted therapies for cancer. Approximately 16% of breast cancer patients have pre-existing diabetes. Breast cancer with type 2 diabetes mellitus (BDM) is provided with its unique biological characteristics and clinical characteristics. This study primarily investigated the therapeutic potential and regulatory mechanism of miR-29a in patients with BDM. Methods: The significance of miR-29a in BDM was analyzed by real-time reverse transcriptase polymerase chain reaction (qRT-PCR) in breast tissues. A cell model for BDM was established by using MDA-MB-231 cells cultured in 3T3-L1 adipocytes cultured with high levels of glucose and insulin. A type 2 diabetes mellitus (T2DM) mouse model was induced in female BALB/c mice through a high-fat diet plus low doses of streptozotocin (STZ). The xenograft mouse-model for BDM was established on these T2DM mouse by using MDA-MB-231 cells. Then the biological effects of miR-29a knockdown mediated by lentivirus-shRNAs on cell proliferation, apoptosis, cell cycle, and migration were investigated. Results: Our results indicated that miR-29a was upregulated in patients with BDM, which correlated with a worse prognosis. In human breast cancer cells, miR-29a knockdown reduced cell proliferation and cell migration and invasion in BDM. In the T2DM xenograft, miR-29a knockdown suppressed MDA-MB-231 cells tumorigenesis and metastasis. We also demonstrated that miR-29a promoted BDM cell growth and metastasis by targeting Sirtuin 1 (SIRT1). Conclusions: Our findings indicated that anti-miR-29a inhibited cell proliferation and invasion in BDM by targeting SIRT1. We believe anti-miR-29a may represent a novel therapeutic approach for the management of patients with BDM.

Targeted Gene Silencing BRAF Synergized Photothermal Effect Inhibits Hepatoma Cell Growth Using New GAL-GNR-siBRAF Nanosystem.

Liver cancer is one of the most common malignancies worldwide. The RAF kinase inhibitors are effective in the treatment of hepatocellular carcinoma (HCC); therefore, inhibition of the BRAF/MEK/ERK pathway has become a new therapeutic strategy for novel HCC therapy. However, targeted specific delivery systems for tumors are still significant obstacle to clinical applications. Galactose (GAL) can target the asialoglycoprotein receptor (ASGPR) that is highly expressed on liver cancer cells. In this study, we designed a novel multifunctional nanomaterial GAL-GNR-siBRAF which consists of three parts, GAL as the liver cancer-targeting moiety, golden nanorods (GNR) offering photothermal capability under near infrared light, and siRNA specifically silencing BRAF (siBRAF). The nanocarrier GAL-GNR-siBRAF showed high siRNA loading capacity and inhibited the degradation of siRNA in serum. Compared with naked gold nanorods, GAL-GNR-siBRAF possessed lower biotoxicity and higher efficacy of gene silencing. Treatment with GAL-GNR-siBRAF significantly downregulated the expression of BRAF and impaired proliferation, migration, and invasion of liver cancer cells. Moreover, combinatorial photothermal effects and BRAF knockdown by GAL-GNR-siBRAF effectively given rise to tumor cell death. Therefore, our study developed a new type of targeted multi-functional nanomaterial GAL-GNR-siBRAF for the treatment of liver cancer, which provides ideas for the development of new clinical treatment methods.