A novel LINC02321 promotes cell proliferation and decreases cisplatin sensitivity in bladder cancer by regulating RUVBL2.

Bladder cancer (BC) has a high incidence and is prone to recurrence. In most instances, the low 5-year survival rate of advanced BC patients results from postoperative recurrence and drug resistance. Long noncoding RNAs (lncRNAs) can participate in numerous biological functions by regulating the expression of genes to affect tumorigenesis. Our previous work had demonstrated that a novel lncRNA, LINC02321, was associated with BC prognosis. In this study, A high expression of LINC02321 was found in BC tissues, which was associated with poor prognosis in patients. LINC02321 promoted both proliferation and G1-G0 progression in BC cells, while also inhibited sensitivity to cisplatin. Mechanistically, LINC02321 can bind to RUVBL2 and regulate the expression levels of RUVBL2 protein by affecting its half-life. RUVBL2 is involved in the DNA damage response. The potential of DNA damage repair pathways to exert chemosensitization has been demonstrated in vivo. The rescue experiment demonstrated that RUVBL2 overexpression can markedly abolish the decreased cell proliferation and the increased sensitivity of BC cells to cisplatin caused by LINC02321 knockdown. The results indicate that LINC02321 functions as an oncogene in BC, and may serve as a novel potential target for controlling BC progression and addressing cisplatin resistance in BC therapy.

Sperm induce macrophage extracellular trap formation via phagocytosis-dependent mechanism.

Infertility is a public health concern worldwide. Asthenozoospermia is a common cause of male infertility and is characterized by decreased motility. Sperm motility ensures that sperm migrate to complete fertilization. Macrophages are an essential component of innate immunity in the female reproductive tract. Macrophage extracellular traps are induced by various microorganisms to capture and mediate the clearance of microorganisms. The relationship between sperm and macrophage extracellular traps is unclear. The human monocyte leukemia (THP-1) cells differentiated by phorbol myristate acetate (PMA) are widely used as surrogate of human macrophages. This study investigated sperm-induced macrophage extracellular trap formation and clarified some of the mechanisms affecting macrophage extracellular trap production. Sperm-induced macrophage extracellular traps were visualized and components of macrophage extracellular traps were identified by immunofluorescence analyses and scanning electron microscopy. By inhibiting macrophage extracellular trap production and macrophage phagocytosis, the relationship between macrophage phagocytosis and macrophage extracellular trap production was analyzed. Sperm could trigger PMA-differentiated THP-1 macrophages to produce extracellular traps. Sperm-triggered macrophage extracellular traps are dependent on phagocytosis and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Sperm from asthenozoospermia donors are more likely to be phagocytosed by macrophages than sperm from healthy donors, which induce more macrophage extracellular trap release. These data confirm the phenomenon and partial mechanism of sperm-induced macrophage extracellular trap formation in vitro. These may partly provide evidence to explain the mechanisms of clearing abnormally morphological or hypomotile sperm in the female reproductive tract and the rationale for the decreased probability of successful fertilization in asthenozoospermia.