Emergence of cancer stem cells in hepatocellular carcinoma

Pilz, Sahra; Schotta, Gunnar

doi:10.15252/embj.201490785

Cited by 1 publication

(1 citation statement)

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“…LCSCs are thought to arise from hepatocyte de-differentiation or transformation from hepatic progenitor cells, and many investigators believe that LCSCs generate and maintain HCC and drive postoperative recurrence [15, 32, 33]. This implies that inhibiting and eliminating LCSCs may be key to reducing recurrence [34, 35].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of microRNA-21 strengthens stem cell-like characteristics in a hepatocellular carcinoma cell line

et al. 2016

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BackgroundLiver cancer stem cells (LCSCs) have been shown to express higher levels of microRNA-21 (miR-21). Here, we examine the possible contributions of miR-21 to the phenotype of LCSCs in culture and in xenograft tumors in nude mice.MethodsThe hepatocellular carcinoma cell line MHCC-97H was stably transformed with a retroviral vector to establish cells overexpressing miR-21, while a cell line transformed with empty vector served as a negative control. RT-PCR and Western blotting were used to evaluate the effects of miR-21 overexpression on the expression of various LCSC markers, a Transwell assay was used to assess the effects on cell migration and invasion, and a spheroid formation assay was used to examine the effects on clonogenesis. The effects of miR-21 overexpression were also examined in tumors in nude mice.ResultsAn MHCC-97H cell line was constructed that stably overexpresses miR-21 at 7.78 ± 1.51-fold higher levels than the negative control cell line. Expression of the LCSC markers CD13, Ep-CAM, CD90, and OCT4 was significantly higher in the miR-21-overexpressing cell line than in the negative control at both mRNA and protein levels. The overexpressing cell line formed larger, tighter, and more numerous spheroids. Overexpression of miR-21 was associated with greater cell migration and invasion. Tumors of overexpressing cells in nude mice had a significantly larger mean volume after 34 days of growth (773.62 ± 163.46 mm3) than tumors of negative control cells (502.79 ± 33.94 mm3, p = 0.048), as well as greater mean weight (0.422 ± 0.019 vs. 0.346 ± 0.006 g, p = 0.003).ConclusionsOverexpression of miR-21 strengthens the phenotype of LCSCs, facilitating invasion, migration, and tumorigenesis in hepatocellular carcinoma.

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