Ferroptosis is an iron‐dependent, lipid peroxide‐driven cell death caused by inhibition of the cystine/glutamate transporter, which is of importance for the survival of triple‐negative breast cancer (TNBC) cells. Erastin is a low molecular weight chemotherapy drug that induces ferroptosis; however, poor water solubility and renal toxicity have limited its application. Exosomes, as drug delivery vehicles with low immunogenicity, high biocompatibility and high efficiency, have attracted increasing attention in recent years. Herein, we developed a formulation of erastin‐loaded exosomes labeled with folate (FA) to form FA‐vectorized exosomes loaded with erastin (erastin@FA‐exo) to target TNBC cells with overexpression of FA receptors. The characterization, drug release, internalization and anti–tumor effect in vitro of erastin@FA‐exo were determined. Erastin@FA‐exo could increase the uptake efficiency of erastin into MDA‐MB‐231 cells; compared with erastin@exo and free erastin, erastin@FA‐exo has a better inhibitory effect on the proliferation and migration of MDA‐MB‐231 cells. Furthermore, erastin@FA‐exo promoted ferroptosis with intracellular depletion of glutathione and reactive oxygen species overgeneration. Western blot analyses revealed that erastin@FA‐exo suppressed expression of glutathione peroxidase 4 (GPX4) and upregulated expression of cysteine dioxygenase (CDO1). We conclude that targeting and biocompatibility of exosome‐based erastin preparations provide an innovative and powerful delivery platform for anti–cancer therapy.

MicroRNAs (miRNAs) play important roles in the cancer development and progression; overexpression of miR-103 has been identified in various tumors. However, its biological function and regulatory mechanism involved in modulation of human gastric cancer (GC) remain largely unknown. This study aimed to confirm clinical significance of miR-103 and investigate its biological role and underlying mechanism in GC. Real-time quantitative PCR (qRT-PCR) revealed miR-103 was highly expressed in GC tissues and cell lines. miR-103 expression was correlated closely with tumor size, Lauren’s classification, and lymph node metastasis. Importantly, Kaplan-Meier analysis revealed that high expression of miR-103 was significantly associated with poor overall survival and disease-free survival of GC patients. Downregulation of miR-103 by transfecting with miR-103 inhibitor significantly suppressed cell proliferation, induced apoptosis, inhibited migration and invasion in vitro and in vivo. Furthermore, miRNA target databases and luciferase reporter assay confirmed that Krüppel-like Factor-4 (KLF4) was a direct target of miR-103 in GC, and there was a significant inverse correlation between miR-103 and KLF4 expression in GC tissues. Moreover, KLF4 downregulation could rescue miR-103’s oncogenic effect on GC cell proliferation, apoptosis, migration, and invasion. Therefore, these results suggested that miR-103 overexpression could contribute to tumor progression by suppressing KLF4, and it might serve as a promising candidate for the prognosis of GC patients.

HSPC159 is a novel human galectin‐related protein that has been shown to be involved in carcinogenesis. Little is known about HSPC159 expression and function in breast cancer. Herein we showed that HSPC159 was aberrantly expressed in both breast cancer cell lines and tumor tissues and that its expression was associated with poor prognosis of breast cancer patients. Using gain‐ and loss‐of‐function methods we found that HSPC159 enhanced breast cancer cell proliferation and metastasis in vitro and in vivo. Mechanistically, HSPC159 was found to induce epithelial‐mesenchymal transition (EMT) and the F‐actin polymerization process of breast cancer cells. Moreover, HSPC159 promoted proliferation, migration and invasion through activating the PI3K/Akt signaling pathway in breast cancer. In conclusion, our findings showed that HSPC159 contributed to breast cancer progression through the PI3K/Akt pathway and might serve as a potential therapeutic target for the treatment of breast cancer.

Background: The RNA-binding protein Zinc Finger Protein 36 like 1(ZFP36L1) plays an important role in regulating the AU-rich elements (AREs) in the 3′ untranslated region (3′ UTR) of mRNAs, indicating a potential link between its expression and cancers. However, the role and mechanism of ZFP36L1 in gastric cancer (GC) are unclear. Objective: This study aimed to explore the role and mechanism of ZFP36L1 in gastric cancer. Material and Method: GC tissue samples and matched normal gastric tissues were collected, and the ZFP36L1 expression in these samples was evaluated by immunohistochemistry analysis. GC cells with different differentiation were selected for in vitro experiments. The ZFP36L1 expression in GC cells was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. The viability and invasiveness of GC cells were assayed by 5-Ethynyl-2-deoxyuridine (EdU) and Transwell assays, respectively. Western blot assay was used to detect the expression of epithelial-to-mesenchymal transition (EMT) related proteins and proteins of the c-Jun N-terminal kinase (JNK) and p38 Mitogen-Activated Protein Kinase (MAPK) signaling pathways. Results: ZFP36L1 is overexpressed in GC tissues. Patients with high ZFP36L1 expression have a poor prognosis. Moreover, ZFP36L1 is overexpressed in the cell lines with a high degree of malig-nancy. ZFP36L1 increases cell proliferation, invasion, and migration in vitro. Furthermore, ZFP36L1 induces EMT. The JNK inhibitor and p38 inhibitor alone or in combination affect the biological function of GC cells. Furthermore, ZFP36L1 promotes GC progression by inhibiting JNK and p38 MAPK signaling pathways. Conclusion: RNA-binding protein ZFP36L1 exerts a role in the occurrence of gastric cancer by the regulation of the JNK and p38 MAPK signaling pathways. The combination of inhibitors of the JNK and p38 MAPK signaling pathways could be a novel treatment strategy for gastric cancer.