Abstract
Research has confirmed that abnormally expressed miRNAs are involved in the occurrence and development of hepatocellular carcinoma (HCC). In the present study, we confirmed that miR‑577 expression both in HCC tissues and cell lines was markedly downregulated. Clinically, downregulated expression of miR‑577 is notably related to malignant clinicopathological features, such as venous invasion and advanced TNM stage. Additionally, miR‑577 may act as a valuable tumor marker to predict the prognosis of HCC patients. Through knockdown and overexpression of miR‑577, miR‑577 was identified as an inhibitor of cell metastatic ability and EMT progress in HCC. Furthermore, miR‑577 was able to directly bind to the 3'‑UTR of homeoboxA1 (HOXA1) to regulate the expression of HOXA1. In addition, there existed a negative correlation between the expression of miR‑577 and HOXA1 in HCC specimens. Rescue experiments revealed that the influence of miR‑577 on the migration, invasion and EMT of HCC cells was reversed by HOXA1. Taken together, our findings demonstrated that miR‑577 functions as an anti‑oncogene to suppress the migration, invasion and EMT of HCC cells through direct interaction with HOXA1. miR‑577 may act as a valuable target for the molecular‑targeted therapy of HCC.
Highlights
As one of the most common malignant tumors, hepatocellular carcinoma (HCC) has been identified as the third primary cause of tumor‐induced death in the word [1]
We found that low miR‐577 expression was notably related to venous invasion (P= 0.007, Table I) as well as advanced tumor‐node‐metastasis (TNM) stage (P= 0.018, Table I)
Downregulation of miR‐577 was closely related to poor clinicopathological characteristics of HCC patients
Summary
As one of the most common malignant tumors, hepatocellular carcinoma (HCC) has been identified as the third primary cause of tumor‐induced death in the word [1]. It is extremely critical to uncover the potential mechanisms underlying HCC progression. MicroRNAs (miRNAs), a type of endogenous, small and non‐coding RNA, are involved in tumor initiation, development and progression via binding with the 3'‐untranslated region (UTR) of target genes, which results in the translational inhibition or degradation of the target mRNAs [5,6]. In research concerning pediatric diabetes, miR‐577 was identified as an inhibitor to pancreatic β‐cell function and survival, which targeted fibroblast growth factor 21 [13]. These studies suggest that miR‐577 is a cancer‐related gene. The expression and the specific mechanism of miR‐577 in HCC remain to be uncovered
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