miR-34a Inhibits Cell Proliferation by Targeting SATB2 in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the most common type of malignancy of the liver and has been reported as the third most frequent cause of cancer associated death worldwide. Accumulating evidence showed that the expression of miR-34a was abnormal in HCC patients; however, the role of miR-34a in HCC is not clear. In this study, we have observed low expression of the miR-34a in both HCC tissues and hepatoma cell line as compared to normal control. Further to investigate the role of miR-34a in HCC development, HepG2 cells were transfected with miR-34a mimic. Following transfection, miR-34a expression was significantly increased, which further repressed proliferation of HepG2 cells. Bioinformatics, Luciferase Reporter, RT-qPCR, and western blotting assays indicated that special AT-rich sequence-binding protein-2 (SATB2) is a direct target of miR-34a in HCC cells. There was a negative correlation between the expression levels of SATB2 and miR-34a. Investigation into the molecular mechanism indicated that miR-34a regulated cell proliferation through inhibiting SATB2. Therefore, the results of the present study may improve understanding regarding the role of miR-34a in regulating cell proliferation and contribute to the development of novel therapy of HCC.

Higher expression of SATB2 in hepatocellular carcinoma of African Americans determines more aggressive phenotypes than those of Caucasian Americans

“…Overexpression of SATB2 rescued the miR‐34a mediated inhibition of cell viability in CSCs. Similarly, in recent studies of HCC, miR‐211 and miR34a levels inversely correlated with SATB2 levels and modulated cancer cell progression and metastasis . Our data demonstrate that SATB2 can regulate cell migration and invasion by modulating EMT‐related genes (cadherins) and transcription factors (Snail, Slug and Zeb1).…”

“…The commonly used markers for the HCC include metastatic carcinomas markers cytokeratins (CK7, CK19 and CK20), neuroendocrine markers (CD56, synaptophysin and chromogranin A) and tissue‐specific markers (SATB2, CDX2, TTF‐1, GCDFP‐15, mammaglobin, etc) . microRNAs (miRNAs) regulate cancer cell progression and metastasis by modulating the expression of SATB2 . Our date showed a negative correlation between the expression levels of SATB2 and miR‐34a in CSCs.…”

“…54 microRNAs (miRNAs) regulate cancer cell progression and metastasis by modulating the expression of SATB2. 25,26 Our date showed a negative correlation between the expression levels of SATB2 and miR-34a in CSCs. Overexpression of SATB2 rescued the miR-34a mediated inhibition of cell viability in CSCs.…”

“…The liver is the first and most common organ to which cancers commonly metastasize and spread in patients. Recent studies have demonstrated the higher expression of SATB2 in the HCC tissues compared with adjacent normal tissues . The commonly used markers for the HCC include metastatic carcinomas markers cytokeratins (CK7, CK19 and CK20), neuroendocrine markers (CD56, synaptophysin and chromogranin A) and tissue‐specific markers (SATB2, CDX2, TTF‐1, GCDFP‐15, mammaglobin, etc) .…”

“…Recent studies have demonstrated the higher expression of SATB2 in the HCC tissues compared with adjacent normal tissues. 25,26,53,54 The commonly used markers for the HCC include metastatic carcinomas markers cytokeratins (CK7, CK19 and CK20), neuroendocrine markers (CD56, synaptophysin and chromogranin A) and tissue-specific markers (SATB2, CDX2, TTF-1, GCDFP-15, mammaglobin, etc). 54 microRNAs (miRNAs) regulate cancer cell progression and metastasis by modulating the expression of SATB2.…”