MicroRNA-26b-5p regulates cell proliferation, invasion and metastasis in human intrahepatic cholangiocarcinoma by targeting S100A7

Abstract

Abstract. The present study aimed to investigate the effects of microRNA expression in intrahepatic cholangiocarcinoma (ICC). It was identified that the expression of microRNA-26b-5p (miR-26b-5p) was downregulated in ICC tissues compared with matched adjacent non-tumor tissues. Furthermore, miR-26b-5p expression was downregulated in metastatic ICC tumor tissues and invasive ICC cell line subpopulations compared with non-metastatic tumor tissue and the parental ICC cells. In vitro studies demonstrated that transfection with an miR-26b-5p mimic inhibited the proliferation, migration and invasion of RBE and HCCC-9810 cells, whereas an miR-26b-5p inhibitor promoted these abilities. S100 calcium-binding protein A7 (S100A7) was predicted as a direct target of miR-26b-5p. Transfection with an miR-26b-5p mimic decreased S100A7 expression, whereas an miR-26b-5p inhibitor increased S100A7 expression. The result of a dual luciferase reporter assay also indicated this interaction. S100A7 was therefore confirmed as a direct target of miR-26b-5p in ICC. The knockdown of S100A7 abrogated the effect of miR-26b-5p on cell migration in RBE and HCCC-9810 cells. In conclusion, the present study demonstrated that miR-26b-5p suppresses the proliferation, migration and invasion of ICC cells by suppressing S100A7.

Friend or Foe: S100 Proteins in Cancer

“…The expression of S100A7 could be downregulated by miR-26b-5p, leading to decreased proliferation, migration, and invasion of intrahepatic cholangiocarcinoma in vitro [241]. Similar effects were observed for miR-24, a miRNA targeting S100A8, which inhibited proliferation and invasion of laryngeal carcinoma cells [242].…”

“…Pre-clinical [239] miR-193a S100A6 S100A6 silencing results in suppression of proliferation, invasion, migration, and angiogenesis within lung cancer models Pre-clinical [240] miR-26b-5p S100A7 S100A7 silencing inhibits proliferation, invasion, and migration of intrahepatic cholangiocarcinoma cells Pre-clinical [241] miR-24 S100A8…”

Identification of MMP9 as a novel key gene in mantle cell lymphoma based on bioinformatic analysis and design of cyclic peptides as MMP9 inhibitors based on molecular docking

“…Invasion and metastasis are important biological chara-cteristics of malignant tumors including MCL. Tumor growth, invasion and metastasis involve a complex multistep process, including the division and proliferation of tumor cells, the degradation of the extracellular matrix, cell escape through the basement membrane, migration into the blood circulation system, tumor cell growth at secondary sites and a series of activities, at the same time accompanied by the formation of new blood vessels ( 4 ). Studies have shown that MMP9, a member of the matrix metalloproteinase (MMP) family is highly expressed in various tumors and plays a major role in the growth, metastasis and angiogenesis of primary and secondary tumors ( 5 – 8 ).…”

Comprehensive Review of Molecular Mechanisms during Cholestatic Liver Injury and Cholangiocarcinoma

“…Specific microRNA segments have been identified to play different roles in the regulations of much pathology [98]. In a published study, the analysis of 80 different liver samples, half of which included tissues with intrahepatic CCA, identified that downregulated microRNA-26b-5p was associated with intrahepatic CCA diagnosis [99]. Additionally, downregulated microRNA-26b-5p correlated with increased invasive capacity of CCA.…”

“…S100 calcium-binding protein A7, which is implicated in the progression of CCA, was found to be a downregulated by microRNA-26b-5p. This is the proposed target that causes the effect of decreased invasion of CCA [99]. MicroRNA-34a is another miRNA that has been found to play a role in the circadian rhythms of humans [100].…”