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.
Long non-coding RNA urothelial cancer associated 1 (UCA1) has been reported to act as a carcinogen in bladder cancer, while its role in diffuse large B-cell lymphoma (DLBCL) remains unclear. The present study was designed to explore the expression pattern and role of UCA1 in DLBCL. The expression pattern of UCA1 and microRNA (miR)-331-3p in DLBCL tissues and cell lines were detected by RT-qPCR. Dual luciferase reporter assay was performed to explore the relationship between UCA1 and miR-331-3p. Cell proliferation was explored by MTT assay. Cell migration and invasion abilities were assessed by Transwell assay. In the present study, it was revealed that the expression of UCA1 was significantly upregulated, while miR-331-3p was downregulated in DLBCL tissues and cell lines. Moreover, UCA1 was revealed to competitively bind with miR-331-3p in DLBCL. Functionally, knockdown of UCA1 was revealed to suppress cell proliferation, migration and invasion in DLBCL cells. Furthermore, upregulation of miR-331-3p prevented cell proliferation, migration and invasion in DLBC cells. In conclusion, the present findings firstly demonstrated that UCA1 silencing restrained DLBCL cell proliferation and metastases viability by suppressing miR-331-3p expression. It is suggested that UCA1 could be a possible medicinal target and biomarker for DLBCL.
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