Cancer stem cells (CSCs) are responsible for the unrestrained cell growth and chemo-resistance of malignant tumors. Reports about miR-33a in different type of cancer are limited, and it remains elusive whether there is a link between miR-33a and chemo-resistance of CSCs. Here we report that Lgr5+ hepatocellular carcinoma (HCC) cells from primary tissues and cell lines behave similarly to CSCs and are chemo-resistant to doxorubicin. Significantly, reduced miR-33a expression is associated with the chemo-resistance of Lgr5+ HCC-CSCs, accompanied by an overexpression of ABCA1 which is identified as target of miR-33a by mainly using miRNA luciferase assay and western-blotting. We demonstrate that down-regulation of miR-33a expression directly contributes to chemo-resistance of Lgr5+ HCC-CSCs, and restoring miR-33a expression sensitizes them to doxorubicin via apoptosis by mainly using TUNEL assay, soft agar colony formation assay and xenograft assay. Additionally, reduced miR-33a expression in HCC tissues is associated with chemo-response and poor patient survival, which suggests the therapeutic potential of miR-33a. In conclusion, our work indicates that ectopic miR-33a expression sensitizes Lgr5+ HCC-CSCs to doxorubicin via direct targeting ABCA1, which sheds new light on understanding the mechanism of chemo-resistance in HCC-CSCs and contributes to development of potential therapeutics against HCC.
Background
Delirium is a common contributor to mortality and hospital costs in stroke patients. Different observational studies have showed inconsistent results regarding the association between cognitive decline/dementia and delirium after acute stroke. Therefore, we performed this meta‐analysis with the aim of determining whether cognitive decline/dementia is related to the risk of delirium after acute stroke.
Methods
We systematically searched PubMed, Embase, Google Scholar, and Web of Science for relevant studies from inception to September 2020. We calculated the pooled odds ratio (OR) with 95% confidence interval (CI) by using fixed or random effects models based on heterogeneity measured by the I2 index.
Results
The association between cognitive decline/dementia and post‐stroke delirium was examined in 13 studies with 3183 participants. After pooled analysis, we found that cognitive decline/dementia was significantly associated with susceptibility to delirium in post‐stroke patients (OR = 3.70, 95%CI: 2.90–4.71, P < 0.001). Subgroup analysis suggested that cognitive decline/dementia was associated with an increased risk of delirium in Caucasians (OR = 3.73, 95%CI: 2.73–5.11, P < 0.001), non‐Caucasians (OR = 3.65, 95%CI: 2.50–5.33, P < 0.001), samples with <200 subjects (OR = 3.70, 95%CI: 2.17–6.31, P < 0.001), samples with ≥200 subjects (OR = 3.70, 95%CI: 2.82–4.85, P < 0.001), studies published in 1990–2009 (OR = 3.17, 95%CI: 1.48–6.77, P = 0.003), and studies published in 2010–2020 (OR = 3.76, 95%CI: 2.92–4.86, P < 0.001).
Conclusions
We identified an association between cognitive decline/dementia and the risk of developing delirium. Cognitive decline/dementia may be a promising predictor for delirium in post‐stroke patients.
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