Archives

  • 2018-07
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • As found in the previous study miR was significantly downreg

    2019-05-27

    As found in the previous study, miR-101 was significantly downregulated in CCA tumors compared with adjacent non-tumor tissues and this was supported by work from another group. This publication also found that miR-101 hepatic levels were decreased in CCA tumors compared with adjacent non-tumor tissues. Furthermore, the authors found that miR-101 levels were decreased in cultured human CCA cells compared with normal cultured cholangiocytes. The role of miR-101 during CCA pathogenesis was further characterized in vitro, and it was noted that VEGFC levels were inversely correlated with miR-101 expression. Overexpression of miR-101 decreased CCA migration and invasion, and administration of VEGFC reversed these effects. This study provides therapeutic insight into the restoration of miR-101 on reversing CCA-associated angiogenesis. Another study looked at the role of miR-21 during CCA proliferation. The study found that in patients with CCA, serum miR-21 levels are drastically increased compared with serum levels in healthy controls, and this finding is partially corroborated by the previous study that found that hepatic miR-21 levels were significantly increased in CCA tumors compared with non-tumor liver tissue. Furthermore, this study showed that inhibition of miR-21 in vitro was able to reduce human CCA cell proliferation through modulation of the jasplakinolide and induction of apoptosis. The authors also found that increased serum levels of miR-21 in CCA patients correlated with adverse clinical features, diminished survival and poor prognosis. These in vitro findings were also supported by another study that found that overexpression of miR-21 in human CCA cells promoted cell growth and migration, whereas inhibition of miR-21 decreased these activities. Overall, these findings not only expand the role that miR-21 plays during CCA growth, but also highlights its usefulness as both a diagnostic tool and therapeutic target. A recent publication analyzed the role of miRNAs during circadian rhythm oscillations and the expression of clock genes in CCA. Circadian rhythm oscillations and the associated clock genes are primarily studied in the central nervous system, but these functions can be seen in peripheral tissues as well as single cells. However, aberrant circadian signaling can lead to tumorigenesis. PCR revealed that the gene expression of PER1, a clock gene, was decreased in cultured CCA cells compared to a normal cholangiocyte cell line, and this was supported by online microarray data showing similar results in human CCA compared with surrounding non-tumor tissue. Protein expression of PER1 was also decreased in human CCA biopsies compared with normal human tissue. Conversely, CCA cells with Per1 overexpression showed decreased proliferation, arrested cell cycle progression and decreased cell migration. The authors hypothesized that Per1 expression may be regulated by miRNAs, and online analysis revealed that the 3′ UTR of PER1 could be targeted by miR-34a. Furthermore, miRNA microarray showed that miR-34a was upregulated in CCA cells compared with normal human liver samples. In vitro the authors inhibited miR-34a expression in CCA cells using a miR inhibitor and then found that the CCA cells had increased PER1 expression. However, when miR-34a was inhibited, CCA cells showed increased PER1 gene expression accompanied with decreased proliferation, arrested cell cycle and decreased cell migration. These findings identify the role of miR-34a as an oncomir during CCA progression via decreased PER1 expression and increased cell proliferation and migration.
    Conclusions and future perspectives The complete determination of the cellular processes that regulate the initiation and progression of cholangiopathies is still widely unknown. Considering the major role that miRNAs play during mRNA expression and function, it is intuitive that these small RNAs could have key roles during cholangiopathy development. However, the specific role of individual miRNAs in the different cholangiopathies remains elusive. When looking at the miRNA expression profiles for each cholangiopathy, there is little overlap in miRNA expression, implying that their expression may be cholangiopathy-specific (Table 1). However, some cholangiopathies do express the same miRNA. For instance, miR-21, a pro-fibrotic miRNA, is upregulated in both BA and CCA, which are known to be fibrosing cholangiopathies, explaining why miR-21 is increased in both BA and CCA. As well, miR-122 expression is upregulated in PSC but is downregulated in CCA. Since miR-122 has been identified as a marker of differentiation it makes sense that this miRNA is decreased in CCA as opposed to PSC. In contrast to miR-122 levels, miR-200c is downregulated in PSC but upregulated in CCA, and previous work has shown that miR-200c increases tumor growth and proliferation, helping to explain this discrepancy in expression. Finally, miR-92a, another miRNA that supports tumor growth, shows decreased expression in PBC but increased expression in BA. This variation in expression may be dependent on the degree of hepatic damage and possible formation of liver cancer in the patients that were analyzed; however, this is not discussed in the referenced manuscripts.