Among patients with triple-negative breast cancer (TNBC), distant metastasis is the leading cause of death. Our previous studies have shown that TNBC progression is greatly facilitated by circKIF4A, but uncertainty remains regarding its role in TNBC brain metastasis and the molecular mechanism. In this study, we found notable upregulation of circKIF4A in TNBC cell lines and brain metastases. Inhibition of circKIF4A impaired the ability of TNBC to proliferate, migrate, and cause brain metastasis. Luciferase reporter assays confirmed that circKIF4A competed for binding to miR-637 with STAT3 3' UTR. Western blot analysis revealed that inhibition of circKIF4A decreased STAT3 and p62 expression, while increased the LC3B-II/LC3B-I ratio and the expression of Beclin, indicating that downregulation of circKIF4A induced autophagy by competing with STAT3 for binding to miR-637. By employing a competitive endogenous RNA (ceRNA) mechanism, the circKIF4A-miR-637-STAT3 axis coordinates brain metastasis in TNBC. circKIF4A can therefore be used as a prognostic biomarker for brain metastasis in TNBC and as a therapeutic target.

This study aims to explore the function and mechanism of G Protein-coupled receptor class C group 5 member A (GPRC5A) in docetaxel-resistance and liver metastasis of breast cancer. Single-cell RNA transcriptomic analysis and bioinformatic analysis are used to screen relevant genes in breast cancer metastatic hepatic specimens. MeRIP, dual-luciferase analysis and bioinformation were used to detect m6A modulation. Mass spectrometry (MS), co-inmunoprecipitation (co-IP) and immunofluorescence colocalization were executed to explore the mechanism of GPRC5A in breast cancer cells. GPRC5A was upregulated in triple-negative breast cancer (TNBC) and was associated with a poor prognosis. In vitro and in vivo experiments demonstrated that knockdown of GPRC5A alleviated metastasis and resistance to docetaxel in TNBC. Overexpression of GPRC5A had the opposite effects. The m6A methylation of GPRC5A mRNA was modulated by METTL3 and YTHDF1, which facilitates its translation. GPRC5A inhibited the ubiquitination-dependent degradation of LAMTOR1, resulting in the recruitment of mTORC1 to lysosomes and activating the mTORC1/p70s6k signaling pathway. METTL3/YTHDF1 axis up-regulates GPRC5A expression by m6A methylation. GPRC5A activates mTORC1/p70s6k signaling pathway by recruiting mTORC1 to lysosomes, consequently promotes docetaxel-resistance and liver metastasis.

Background: Metastasis of breast cancer have caused the majority of cancer-related death worldwide. The circRNAs are associated with tumorigenesis and metastasis in breast cancer according to recent research. However, the biological mechanism of circRNAs in liver metastatic breast cancer remains ambiguous yet. Methods: Microarray analysis of three pairs of primary BC tissues and matched hepatic metastatic specimens identified circEZH2. We used RT-qPCR and FISH assays to confirm circEZH2 existence, characteristics, and expression. Both in vivo and in vitro, circEZH2 played an oncogenic role which promoted metastasis as well. A range of bioinformatic analysis, Western blot, RNA pull-down, RIP, ChIP, and animal experiments were used to define the feedback loop involving FUS, circEZH2, miR-217-5p, KLF5, FUS, CXCR4 as well as epithelial and mesenchymal transition. Results: In our research, circEZH2 was proved to be upregulated in liver metastases in BC and predicted the worse prognosis in breast cancer patients. Overexpression of circEZH2 notably accentuated the vitality and invasion of BC cells, whereas knockdown of circEZH2 elicited the literally opposite effects. Besides, overexpressed circEZH2 promoted tumorigenesis and liver metastasis in vivo. Moreover, circEZH2 could adsorb miR-217-5p to upregulate KLF5 thus leading to activate FUS transcription which would facilitate the back-splicing program of circEZH2. Meanwhile, KLF5 could upregulated CXCR4 transcriptionally to accelerate epithelial and mesenchymal transition of breast cancer. Conclusions: Consequently, a novel feedback loop FUS/circEZH2/KLF5/CXCR4 was established while circEZH2 could be novel biomarker and potential target for BC patients’ therapy.

Breast cancer is the most common type of malignancy among women. Due to the iron-dependent character of breast cancer cells, they are more sensitive to ferroptosis compared to normal cells. It is possible to reverse tumor resistance by inducing ferroptosis in breast cancer cells, thereby improving tumor treatment outcomes. Ferroptosis is highly dependent on the balance of oxidative and antioxidant status. When ferroptosis occurs, intracellular iron levels are significantly increased, leading to increased membrane lipid peroxidation and ultimately triggering ferroptosis. Ferroptotic death is a form of autophagy-associated cell death. Synergistic use of nanoparticle-loaded ferroptosis-inducer with radiotherapy and chemotherapy achieves more significant tumor suppression and inhibits the growth of breast cancer by targeting cancer tissues, enhancing the sensitivity of cells to drugs, reducing the drug resistance of cancer cells and the toxicity of drugs. In this review, we present the current status of breast cancer and the mechanisms of ferroptosis. It is hopeful for us to realize effective treatment of breast cancer through targeted ferroptosis.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumours of the head and neck in Southeast Asia and southern China. The Phosphatidylinositol 3-kinase/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway is involved in processes related to tumour initiation/progression, such as proliferation, apoptosis, metastasis, and drug resistance, and is closely related to the clinicopathological features of NPC. In addition, key genes involved in the PI3K/AKT/mTOR signalling pathway undergo many changes in NPC. More interestingly, a growing body of evidence suggests an interaction between this signalling pathway and microRNAs (miRNAs), a class of small noncoding RNAs. Therefore, in this review, we discuss the interactions between key components of the PI3K/AKT/mTOR signalling pathway and various miRNAs and their importance in NPC pathology and explore potential diagnostic biomarkers and therapeutic targets.