miR‐221, an oncogenic microRNA, can promote cell proliferation and is highly expressed in various types of tumors. However, the role of exosomal miR‐221 in benzene‐caused carcinogenesis remains elusive. Our study was designed to investigate whether exosomes secreted by the hydroquinone (HQ; an active metabolite of benzene)‐transformed malignant cells can transmit miR‐221 to normal recipient cells and its possible effects on cell viability. Our investigation revealed that expression levels of miR‐221 were significantly increased in HQ‐transformed malignant cells relative to normal controls. Furthermore, exposure of control cells to exosomes that were derived from HQ‐transformed malignant cells increased miR‐221 levels and promoted their proliferation. Analyses of the biological potency of exosomes derived from HQ‐transformed malignant cells in which miR‐221 levels were decreased using an inhibitor, showed that both miR‐221 levels and proliferation of recipient cells were decreased, but still were higher than those of normal 16HBE cells. Our study indicates that exosomal miR‐221 derived from HQ‐transformed malignant human bronchial epithelial cells is involved in the proliferation of recipient cells.
Introduction Triple-negative breast cancer (TNBC) is currently the most malignant subtype of breast cancer without effective targeted therapies. DNAJB4 (Dnaj heat shock protein family (Hsp40) member B4) is a member of the human heat shock protein family (Hsp40). The clinical significance of DNAJB4 in breast cancer has been reported in our previous study. However, the biological function of DNAJB4 in TNBC cell apoptosis remains unclear to date. Methods The expression of DNAJB4 in normal breast cells, breast cancer cells, four-paired TNBC tissues, and adjacent noncancerous tissues was quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay. The role of DNAJB4 in TNBC cell apoptosis was investigated using a number of gain- and loss-of-function in vitro and in vivo assays. The underlying molecular mechanisms in TNBC cell apoptosis were elucidated via Western blot assay. Results DNAJB4 expression was significantly downregulated in TNBC tissues and cell lines. DNAJB4 knockdown inhibited TNBC cell apoptosis and promoted tumorigenicity in vitro and in vivo, but DNAJB4 overexpression resulted in the opposite. Mechanically, DNAJB4 knockdown inhibited TNBC cell apoptosis through suppression of the Hippo signaling pathway, and the result was reversed after DNAJB4 overexpression. Conclusions DNAJB4 promotes TNBC cell apoptosis by activating the Hippo signaling pathway. Therefore, DNAJB4 may act as a prognostic biomarker and therapeutic target for TNBC.
Temozolomide (TMZ), a therapeutic DNA alkylator that can cause lethal DNA damage in cancer cells, is widely used for the standard chemotherapy against glioblastoma. However, long‐term treatment with TMZ often causes drug resistance and poor prognosis, the mechanism of which remains largely unclear. This study aimed to investigate the possible role of miR‐222/GAS5 axis on DNA damage and cytotoxic effects induced by TMZ in glioblastoma cells (T98G). Data suggest that the DNA comet tail length of T98G is positively correlated with the levels of miR‐222 (R2 = 0.9808, P < 0.05), and negatively correlated with the levels of GAS5 (R2 = 0.8903, P < 0.05). The optical density value of T98G is negatively correlated with the levels of miR‐222 (R2 = 0.7848, P < 0.05), and positively correlated with the levels of GAS5 (R2 = 0.6886, P < 0.05). Furthermore, comet tail length and optical density value are negatively and positively correlated with the levels of O‐6‐methylguanine‐DNA methyltransferase, respectively (R2 = 0.8462, P < 0.05; R2 = 0.7018, P < 0.05). In conclusion, miR‐222/GAS5 is involved in DNA damage and cytotoxic effects induced by TMZ, which means that miR‐222/GAS5 may have great potential of being used as a biomarker for screening of chemotherapeutic alkylators.
Salvianolic acid B (Sal B) has previously reported anti-hepatic fibrosis effects, though it is not clear if it can inhibit hepatic fibrosis by regulating the hedgehog (Hh) signaling pathway. The aim of the present study was to explore the roles and mechanism of Sal B in preventing and treating liver fibrosis in rats. The study also aimed to determine the role of the Hh signaling pathway in this process. A rat model of liver fibrosis was induced through the subcutaneous injection of 50% carbon tetrachloride, followed by treatment with Sal B. After gavage, blood was collected to detect serum markers of liver injury. The degree of liver fibrosis and tissue damage was assessed using histopathological analysis. Western blotting and reverse transcription-quantitative PCR were used to detect the expression levels of TGF-β1 and Hh signaling pathway-related genes, including Sonic hedgehog (Shh) protein, membrane protein receptor protein patched homolog 1 (Ptch1), membrane protein receptor Smoothened (Smo) and transcription factor glioma-associated oncogene homolog 1 (Gli1). Serum alanine aminotransferase, aspartate aminotransferase and total bilirubin levels were decreased, whilst levels of albumin were increased in rats with liver fibrosis that were treated with Sal B (P<0.05). Additionally, significant increases in TGF-β1, Shh, Ptch1, Smo, Gli1 and α-smooth muscle actin expression levels were observed in the liver tissues of rats with hepatic fibrosis (P<0.05). However, Sal B treatment significantly reduced the expression levels of these proteins (P<0.05). In conclusion, the results of the present study suggested that the Hh signaling pathway may be activated during the process of rat liver fibrosis. Thus, Sal B may exert its anti-hepatic fibrosis effects, at least in part, by inhibiting the activation of the Hh signaling pathway.
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