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In this study, it is found that the lncRNA, DNA damage inducible transcript 4 antisense RNA1 (DDIT4-AS1), is highly expressed in triple-negative breast cancer (TNBC) cell lines and tissues due to H3K27 acetylation in the promoter region, and promotes the proliferation, migration, and invasion of TNBC cells via activating autophagy. Mechanistically, it is shown that DDIT4-AS1 induces autophagy by stabilizing DDIT4 mRNA via recruiting the RNA binding protein AUF1 and promoting the interaction between DDIT4 mRNA and AUF1, thereby inhibiting mTOR signaling pathway. Furthermore, silencing of DDIT4-AS1 enhances the sensitivity of TNBC cells to chemotherapeutic agents such as paclitaxel both in vitro and in vivo. Using a self-activatable siRNA/drug core-shell nanoparticle system, which effectively deliver both DDIT4-AS1 siRNA and paclitaxel to the tumor-bearing mice, a significantly enhanced antitumor activity is achieved. Importantly, the codelivery nanoparticles exert a stronger antitumor effect on breast cancer patient-derived organoids. These findings indicate that lncRNA DDIT4-AS1-mediated activation of autophagy promotes progression and chemoresistance of TNBC, and targeting of DDIT4-AS1 may be exploited as a new therapeutic approach to enhancing the efficacy of chemotherapy against TNBC.

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Cisplatin has been reported to promote the expression of programmed cell death ligand-1 (PD-L1) in some cancer cells. However, the underlying mechanism through which PD-L1 is transcriptionally regulated by cisplatin in hepatocellular carcinoma (HCC) cells remains largely unknown. In the present study, we found that the expression of hepatocyte growth factor (HGF), p-Akt, p-ERK, and PD-L1 was increased in cisplatin-treated SNU-368 and SNU-739 cells. HGF stimulation also increased PD-L1 expression in these cells. Moreover, Inhibition of HGF/c-MET, PI3K/Akt, and MEK/ERK signaling pathways can dramatically block cisplatin or HGF-induced PD-L1 expression in SNU-368 and SNU-739 cells. In vivo, combination PHA665752 with cisplatin significantly reduced tumor weight with increased infiltration of CD8+ T cells in the tumor. Taken together, our study suggested that HGF/c-Met axis-induced the activation of PI3K/Akt and MEK/ERK pathways contributes to cisplatin-mediated PD-L1 expression. These findings may provide an alternative avenue for the treatment of HCC.

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We analyze the source of the position deviation and propose a demodulation recursive compensation algorithm to ensure a sub-millimeter resolution in improved optical frequency domain reflectometry. The position deviation between the geometric path and optical path changes with the temperature or strain, due to the elastic-optic and thermal-optic effects. It accumulates along the fiber and becomes large enough to affect the spectral correlation between the measured and reference spectra at the fiber end. The proposed algorithm compensates for the position deviation of each measuring point and aligns the measured spectra with its reference. The numerical and experimental results both reveal that the signal-to-noise ratio of the correlation is improved doubly and a sub-millimeter spatial resolution becomes available at a 30 m fiber end. The recursive compensation algorithm helps to restrain the correlation degeneration at the fiber end and promises an effective approach to a sub-millimeter resolution in optical frequency domain reflectometry.