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MicroRNA-212 inhibits hepatocellular carcinoma cell proliferation and induces apoptosis by targeting FOXA1.

Tu H, Wei G, Cai Q, Chen X, Sun Z, Cheng C, Zhang L, Feng Y, Zhou H, Zhou B, Zeng T - Onco Targets Ther (2015)

Bottom Line: In this study, the miR-212 expression was found to be obviously downregulated in hepatocellular carcinoma (HCC) tissues as compared with adjacent nontumor tissues.Interestingly, we found that upregulation of miR-212 decreased FOXA1 expression in HepG2 cells.In conclusion, miR-212 is a potent prognostic marker and may suppress HCC tumor growth by inhibiting FOXA1 expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, Hubei University of Medicine, Shiyan, People's Republic of China.

ABSTRACT
MircroRNA-212 (miR-212) is proposed as a novel tumor-related miRNA and has been found to be significantly deregulated in human cancers. In this study, the miR-212 expression was found to be obviously downregulated in hepatocellular carcinoma (HCC) tissues as compared with adjacent nontumor tissues. Clinical association analysis indicated that low expression of miR-212 was prominently correlated with poor prognostic features of HCC, including high AFP level, large tumor size, high Edmondson-Steiner grading, and advanced tumor-node-metastasis tumor stage. Furthermore, the miR-212 expression was an independent prognostic marker for predicting both 5-year overall survival and disease-free survival of HCC patients. Our in vitro studies showed that upregulation of miR-212 inhibited cell proliferation and induced apoptosis in HepG2 cells. On the contrary, downregulation of miR-212 promoted cell proliferation and suppressed apoptosis in Huh7 cells. Interestingly, we found that upregulation of miR-212 decreased FOXA1 expression in HepG2 cells. Significantly, FOXA1 was identified as a direct target of miR-212 in HCC. FOXA1 was downregulated in HCC tissues as compared with noncancerous tissues. An inverse correlation between FOXA1 and miR-212 expression was observed in HCC tissues. Notably, FOXA1 knockdown inhibited cell proliferation and induced apoptosis in HepG2 cells. In conclusion, miR-212 is a potent prognostic marker and may suppress HCC tumor growth by inhibiting FOXA1 expression.

No MeSH data available.


Related in: MedlinePlus

miR-212 is inversely correlated with FOXA1 in HCC.Notes: (A) Comparing differences in the expression levels of FOXA1 between HCC (T) and matched adjacent nontumor tissues (NT), *P<0.05. (B) Representative immunostaining showed negative expression of FOXA1 in miR-212 high-expressing HCC tissue and positive expression of FOXA1 in miR-212 low-expressing tumor. A significant inverse correlation between miR-212 and FOXA1 expression was observed in HCC tissues. Scale bar: 50 µm, *P<0.05.Abbreviations: FOXA1, forkhead box protein A1; HCC, hepatocellular carcinoma; IHC, immunohistochemistry; miR-212, microRNA 212.
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f4-ott-8-2227: miR-212 is inversely correlated with FOXA1 in HCC.Notes: (A) Comparing differences in the expression levels of FOXA1 between HCC (T) and matched adjacent nontumor tissues (NT), *P<0.05. (B) Representative immunostaining showed negative expression of FOXA1 in miR-212 high-expressing HCC tissue and positive expression of FOXA1 in miR-212 low-expressing tumor. A significant inverse correlation between miR-212 and FOXA1 expression was observed in HCC tissues. Scale bar: 50 µm, *P<0.05.Abbreviations: FOXA1, forkhead box protein A1; HCC, hepatocellular carcinoma; IHC, immunohistochemistry; miR-212, microRNA 212.

Mentions: The expression of FOXA1 was further detected using immunohistochemistry in the previous cohort of 86 HCC specimens. FOXA1 was demonstrated to be significantly higher in HCC tissues as compared with that in noncancerous tissues (P<0.05, Figure 4A). The immunoreactivity of FOXA1 was considered either negative (score 0) or positive (scores 1–3). In these cases, the expression of FOXA1 was detected in 69.8% (30/43) of the HCC samples with low expression of miR-212, whereas only 34.9% (15/43) of the HCC specimens with high expression of miR-212 showed a positive FOXA1 signal (P<0.05, Figure 4B). Furthermore, Spearman correlation analysis indicated that miR-212 was inversely correlated with FOXA1 expression in HCC tissues (r=−0.562, P<0.001).


MicroRNA-212 inhibits hepatocellular carcinoma cell proliferation and induces apoptosis by targeting FOXA1.

Tu H, Wei G, Cai Q, Chen X, Sun Z, Cheng C, Zhang L, Feng Y, Zhou H, Zhou B, Zeng T - Onco Targets Ther (2015)

miR-212 is inversely correlated with FOXA1 in HCC.Notes: (A) Comparing differences in the expression levels of FOXA1 between HCC (T) and matched adjacent nontumor tissues (NT), *P<0.05. (B) Representative immunostaining showed negative expression of FOXA1 in miR-212 high-expressing HCC tissue and positive expression of FOXA1 in miR-212 low-expressing tumor. A significant inverse correlation between miR-212 and FOXA1 expression was observed in HCC tissues. Scale bar: 50 µm, *P<0.05.Abbreviations: FOXA1, forkhead box protein A1; HCC, hepatocellular carcinoma; IHC, immunohistochemistry; miR-212, microRNA 212.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556035&req=5

f4-ott-8-2227: miR-212 is inversely correlated with FOXA1 in HCC.Notes: (A) Comparing differences in the expression levels of FOXA1 between HCC (T) and matched adjacent nontumor tissues (NT), *P<0.05. (B) Representative immunostaining showed negative expression of FOXA1 in miR-212 high-expressing HCC tissue and positive expression of FOXA1 in miR-212 low-expressing tumor. A significant inverse correlation between miR-212 and FOXA1 expression was observed in HCC tissues. Scale bar: 50 µm, *P<0.05.Abbreviations: FOXA1, forkhead box protein A1; HCC, hepatocellular carcinoma; IHC, immunohistochemistry; miR-212, microRNA 212.
Mentions: The expression of FOXA1 was further detected using immunohistochemistry in the previous cohort of 86 HCC specimens. FOXA1 was demonstrated to be significantly higher in HCC tissues as compared with that in noncancerous tissues (P<0.05, Figure 4A). The immunoreactivity of FOXA1 was considered either negative (score 0) or positive (scores 1–3). In these cases, the expression of FOXA1 was detected in 69.8% (30/43) of the HCC samples with low expression of miR-212, whereas only 34.9% (15/43) of the HCC specimens with high expression of miR-212 showed a positive FOXA1 signal (P<0.05, Figure 4B). Furthermore, Spearman correlation analysis indicated that miR-212 was inversely correlated with FOXA1 expression in HCC tissues (r=−0.562, P<0.001).

Bottom Line: In this study, the miR-212 expression was found to be obviously downregulated in hepatocellular carcinoma (HCC) tissues as compared with adjacent nontumor tissues.Interestingly, we found that upregulation of miR-212 decreased FOXA1 expression in HepG2 cells.In conclusion, miR-212 is a potent prognostic marker and may suppress HCC tumor growth by inhibiting FOXA1 expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, Hubei University of Medicine, Shiyan, People's Republic of China.

ABSTRACT
MircroRNA-212 (miR-212) is proposed as a novel tumor-related miRNA and has been found to be significantly deregulated in human cancers. In this study, the miR-212 expression was found to be obviously downregulated in hepatocellular carcinoma (HCC) tissues as compared with adjacent nontumor tissues. Clinical association analysis indicated that low expression of miR-212 was prominently correlated with poor prognostic features of HCC, including high AFP level, large tumor size, high Edmondson-Steiner grading, and advanced tumor-node-metastasis tumor stage. Furthermore, the miR-212 expression was an independent prognostic marker for predicting both 5-year overall survival and disease-free survival of HCC patients. Our in vitro studies showed that upregulation of miR-212 inhibited cell proliferation and induced apoptosis in HepG2 cells. On the contrary, downregulation of miR-212 promoted cell proliferation and suppressed apoptosis in Huh7 cells. Interestingly, we found that upregulation of miR-212 decreased FOXA1 expression in HepG2 cells. Significantly, FOXA1 was identified as a direct target of miR-212 in HCC. FOXA1 was downregulated in HCC tissues as compared with noncancerous tissues. An inverse correlation between FOXA1 and miR-212 expression was observed in HCC tissues. Notably, FOXA1 knockdown inhibited cell proliferation and induced apoptosis in HepG2 cells. In conclusion, miR-212 is a potent prognostic marker and may suppress HCC tumor growth by inhibiting FOXA1 expression.

No MeSH data available.


Related in: MedlinePlus