MicroRNA‑584 prohibits hepatocellular carcinoma cell proliferation and invasion by directly targeting BDNF

Abstract

in recent decades, an increasing number of studies have demonstrated that numerous micrornas (mirnas) are dysregulated in hepatocellular carcinoma (Hcc); these aberrantly expressed mirnas are contributing regulators of Hcc formation and progression. Thus, revealing the biological roles of mirnas in Hcc may provide novel information on the identification of effective therapeutic targets and valuable diagnosis methods. Herein, reverse transcription-quantitative Pcr was performed to determine the expression profile of miRNA-584 (miR-584) in HCC tissues and cell lines. Cell Counting Kit-8 and cell invasion assays were utilized to evaluate the influence of mIR-584 overexpression on HCC cell proliferation and invasion, respectively. The present study demonstrated that miR-584 expression was reduced in Hcc tissues and cell lines compared with normal controls. clinical analysis indicated that decreased miR-584 expression was significantly associated with tumor size, TnM stage and lymph node metastasis of patients with HCC. Additionally, resumption of miR-584 expression inhibited proliferation and invasion of Hcc cells. Mechanistically, it was demonstrated that miR-584 can directly interact with the 3'-untranslated regions of brain-derived neurotrophic factor (BdnF) mrna, and reduce its mrna and protein levels in Hcc cells. Furthermore, BdnF was upregulated in Hcc tissues, and its level was inversely correlated with miR-584 expression. notably, restored BdnF expression antagonized the inhibitory effects of miR-584 overexpression on HCC cells. In conclusion, miR-584 may serve tumor-suppressive roles in HCC by directly targeting BDNF, thus suggesting that miR-584 may serve as a potential candidate for treatment of patients with this disease.

MYC‐activated LINC00607 promotes hepatocellular carcinoma progression by regulating the miR‐584‐3p/ROCK1 axis

“…MicroRNAs (miRNAs) regulate the progress of many kinds of tumors, and lncRNA was found to be the “molecular sponge” of miRNA 35–37 . SNHG14 regulates miR‐876‐5p in HCC 25 ; LOC101927746 inhibits miR‐584‐3p in colorectal cancer 38 ; miR‐584 targets BDNF in hepatocellular carcinoma 39 . In our research, we identified a new downstream miR‐584‐3p of LINC00607 .…”

“…LOC101927746 inhibits miR-584-3p in colorectal cancer 38 ; miR-584 targets BDNF in hepatocellular carcinoma. 39 In our research, we identified a new downstream miR-584-3p of LINC00607. Moreover, we conducted luciferase reporter assay, RNA immunoprecipitation and qPCR to verify that LINC00607 could directly target miR-584-3p to promote HCC progression, and we identified ROCK1 as a miR-584-3p target; we also conducted luciferase reporter assay to verify miR-584-3p binding to ROCK1 3 0 UTR.…”

BDNF Modulation by microRNAs: An Update on the Experimental Evidence

“…Together, those findings suggest that a mechanistic crosstalk between inflammation in peripheral tissues and neurodegenerative conditions in the CNS might be driven by microRNAs. miR-584, miR-744, miR-26a-1, and miR-26a-2 subtypes [24,28,58,60,72,75,78,88,93,94,96,102,112,125,126,128,132,133,137,190]. The evidence that miR-206 is able to suppress BDNF synthesis in diverse tissues such as the cardiac muscles, the skeletal muscles, and the endothelial tissue elucidates a role for microRNAs in tissuetissue communication, although their actions might be locally regulated [30,43,45,48,61,92,102,115,120,139,142,169,171,177,191].…”

“…A great part of the research identifying BDNF-target microRNAs concerns investigations on the oncogenicity of BDNF/TrkB signal transduction in tumor cell growth and metastasis [188,189]. A list of microRNAs found to degrade BDNF mRNA transcripts in oncology research is as follows: miR-10a, miR-22, miR-204, miR-107, miR-382, miR-496, miR-497, miR-584, miR-744, miR-26a-1, and miR-26a-2 subtypes [24,28,58,60,72,75,78,88,93,94,96,102,112,125,126,128,132,133,137,190]. The evidence that miR-206 is able to suppress BDNF synthesis in diverse tissues such as the cardiac muscles, the skeletal muscles, and the endothelial tissue elucidates a role for microRNAs in tissue-tissue communication, although their actions might be locally regulated [30,43,45,48,61,92,102,115,120,139,142,169,171,177,191].…”