MicroRNA-155 promotes tumor growth of human hepatocellular carcinoma by targeting ARID2

Abstract

Aberrant expression of microRNA-155 (miR-155) has been reported in several human cancers and is associated with prognosis of patients. However, the clinical significance of miR‑155 and its underlying mechanisms involved in hepatocarcinogenesis remain to be determined. In this study, we demonstrated that the expression of miR-155 was elevated in both hepatocellular carcinoma (HCC) tissues and cell lines. Clinical association analysis revealed that high expression of miR-155 was correlated with malignant clinicopathological characteristics including large tumor size, high Edmondson-Steiner grading and TNM tumor stage. Furthermore, its high expression conferred a reduced 5-year overall survival and disease-free survival of HCC patients. Gain- and loss-of function studies revealed that miR‑155 promoted cell cycle progression, cell proliferation and inhibited apoptosis. Mechanistically, we identified AT-rich interactive domain 2 (ARID2) as a direct downstream target and functional mediator of miR‑155 in HCC cells. Notably, alterations of ARID2 expression abrogated the effects of miR‑155 on HCC cell proliferation, cell cycle and apoptosis. Moreover, we demonstrated that Akt phosphorylation is essential for the functional roles of miR‑155 through altering Cyclin D1 and p27, which were key components of cell cycle machinery. Finally, we disclosed that the downregulation of miR‑155 suppressed tumor growth of HCC by inhibiting Akt signaling pathway. In conclusion, our results indicate that miR‑155 promotes tumor growth of HCC by targeting ARID2-mediated Akt phosphorylation pathway, and potentially serves as a novel prognostic biomarker and therapeutic target for HCC.

miR‐155 overexpression is followed by downregulation of its target gene, NFE2L2, and altered pattern of VEGFA expression in the liver of melanoma B16‐bearing mice at the premetastatic stage

“…Our previous study found miR‐155 to be the most notably upregulated and miR‐205 the most notably downregulated microRNAs in melanoma, as compared with benign melanocytic tumours . Those data are in accordance with several studies reporting the role of miR‐155 as an oncogene and that of miR‐205‐5p as an oncosuppressor in various types of cancer . Taken together, these findings prompted us to further investigate the target genes of miR‐155 and miR‐205.…”

MicroRNA‐155‐5p promotes hepatocellular carcinoma progression by suppressing PTEN through the PI3K/Akt pathway

“…MicroRNA (miR) are small (19–22 nucleotides [nts]) RNA molecules and play crucial functions in the regulation of important processes, such as development, proliferation, differentiation, apoptosis and stress responses . Among these, miR‐155 is a well‐characterized miR and has been proven to participate in inflammatory responses, immune system regulation, hematologic system disorder, cardiovascular diseases and tumorigenesis . MiR‐155 is located on human chromosome 21q21.3 and was first identified as a frequent integration site of the avian leucosis virus .…”

HBx protein‐mediated ATOH1 downregulation suppresses ARID2 expression and promotes hepatocellular carcinoma

“…Several groups have reported that ARID2 loss‐of‐function mutations are related to tumor progression and poor survival in patients with HCC and gastric carcinoma . A recent study showed that microRNA‐155 accelerates hepatoma growth through targeting of the ARID2‐mediated Akt phosphorylation pathway . However, little is known about the functional role of ARID2 in HCC, especially in the context of HBV replication.…”

“…(36) A recent study showed that microRNA-155 accelerates hepatoma growth through targeting of the ARID2-mediated Akt phosphorylation pathway. (37) However, little is known about the functional role of ARID2 in HCC, especially in the context of HBV replication.…”