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MicroRNA-431 inhibits migration and invasion of hepatocellular carcinoma cells by targeting the ZEB1-mediated epithelial-mensenchymal transition.

Sun K, Zeng T, Huang D, Liu Z, Huang S, Liu J, Qu Z - FEBS Open Bio (2015)

Bottom Line: Herein, we found that miR-431 expression was reduced in HCC tissues compared to noncancerous tissues.We found that up-regulation of miR-431 expression decreased zinc finger E-box binding homeobox 1 (ZEB1) expression and inhibited the epithelial-mesenchymal transition (EMT) with increased E-cadherin expression and decreased vimentin expression in HCCLM3 cells.In conclusion, miR-431 inhibits migration and invasion of HCC cells by suppressing ZEB1-mediated EMT.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China.

ABSTRACT
MicroRNA-431 (miR-431) has been recognized as an oncogenic miRNA, being implicated in the initiation and development of human cancers. Recently, deregulation of miR-431 has been reported in several tumors. However, the clinical significance of miR-431 and its underlying role in human hepatocellular carcinoma (HCC) are poorly explored. Herein, we found that miR-431 expression was reduced in HCC tissues compared to noncancerous tissues. Otherwise, down-regulation of miR-431 was observed in aggressive tumor tissues. The levels of miR-431 expression in HCC cell lines were significantly lower than that in a nontransformed hepatic cell line. Clinical association analyses disclosed that a low level of miR-431 was prominently associated with poor prognostic features of HCC including venous infiltration, high Edmondson-Steiner grading and advanced tumor-node-metastasis (TNM) tumor stage. Our in vitro studies showed that up-regulation of miR-431 expression reduced cell invasion and migration in HCCLM3 cells. In contrast, down-regulation of miR-431 expression promoted SMMC-7721 cell invasion and migration. We found that up-regulation of miR-431 expression decreased zinc finger E-box binding homeobox 1 (ZEB1) expression and inhibited the epithelial-mesenchymal transition (EMT) with increased E-cadherin expression and decreased vimentin expression in HCCLM3 cells. Otherwise, down-regulation of miR-431 expression increased ZEB1 expression and promoted EMT in SMMC-7721 cells. Significantly, ZEB1 was identified as a target of miR-431 in HCC. ZEB1 knockdown abrogated the effect of miR-431 silencing on EMT and cell mobility in SMMC-7721 cells. In conclusion, miR-431 inhibits migration and invasion of HCC cells by suppressing ZEB1-mediated EMT.

No MeSH data available.


Related in: MedlinePlus

The expression levels of miR-431 in HCC tissues and cells. Comparing differences in the expression levels of miR-431 between (A) HCC (n = 86) and matched nontumor tissues (n = 86), (B) aggressive (n = 18) and nonaggressive tumor tissues (n = 68), (C) HCC tissues arising from recurrent (n = 41) and non-recurrent groups (n = 45), and (D) HCC cell lines with different metastatic potentials and the immortalized hepatic cell line LO2 (n = 6). ∗P < 0.05.
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f0005: The expression levels of miR-431 in HCC tissues and cells. Comparing differences in the expression levels of miR-431 between (A) HCC (n = 86) and matched nontumor tissues (n = 86), (B) aggressive (n = 18) and nonaggressive tumor tissues (n = 68), (C) HCC tissues arising from recurrent (n = 41) and non-recurrent groups (n = 45), and (D) HCC cell lines with different metastatic potentials and the immortalized hepatic cell line LO2 (n = 6). ∗P < 0.05.

Mentions: The mean level of miR-431 expression in HCC was obviously lower than that in matched tumor-adjacent tissues (P < 0.05, Fig. 1A). Aggressive HCCs were defined as cases with intrahepatic spreading, venous infiltration or tumor invasion into bile ducts. By contrast with nonaggressive HCCs, the expression of miR-431 was obviously reduced in aggressive cases (P < 0.05, Fig. 1B). Otherwise, the expression of miR-431 was significantly decreased in tumor tissues arising from patients suffered recurrence (P < 0.05, Fig. 1C). Taken together, reduced expression of miR-431 was associated with aggressive HCCs. Next, we found that miR-431 was obviously down-regulated in HCC cells compared with normal hepatic cells (P < 0.05, Fig. 1D). In addition, the expression of miR-431 in highly invasive HCC cell lines, MHCC97H and HCCLM3, were obviously lower than those in low invasive ones including SMMC-7721 and Hep3B (P < 0.05, Fig. 1D). These results demonstrate that reduced expression of miR-431 facilitates metastatic behavior of HCC cells.


MicroRNA-431 inhibits migration and invasion of hepatocellular carcinoma cells by targeting the ZEB1-mediated epithelial-mensenchymal transition.

Sun K, Zeng T, Huang D, Liu Z, Huang S, Liu J, Qu Z - FEBS Open Bio (2015)

The expression levels of miR-431 in HCC tissues and cells. Comparing differences in the expression levels of miR-431 between (A) HCC (n = 86) and matched nontumor tissues (n = 86), (B) aggressive (n = 18) and nonaggressive tumor tissues (n = 68), (C) HCC tissues arising from recurrent (n = 41) and non-recurrent groups (n = 45), and (D) HCC cell lines with different metastatic potentials and the immortalized hepatic cell line LO2 (n = 6). ∗P < 0.05.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664716&req=5

f0005: The expression levels of miR-431 in HCC tissues and cells. Comparing differences in the expression levels of miR-431 between (A) HCC (n = 86) and matched nontumor tissues (n = 86), (B) aggressive (n = 18) and nonaggressive tumor tissues (n = 68), (C) HCC tissues arising from recurrent (n = 41) and non-recurrent groups (n = 45), and (D) HCC cell lines with different metastatic potentials and the immortalized hepatic cell line LO2 (n = 6). ∗P < 0.05.
Mentions: The mean level of miR-431 expression in HCC was obviously lower than that in matched tumor-adjacent tissues (P < 0.05, Fig. 1A). Aggressive HCCs were defined as cases with intrahepatic spreading, venous infiltration or tumor invasion into bile ducts. By contrast with nonaggressive HCCs, the expression of miR-431 was obviously reduced in aggressive cases (P < 0.05, Fig. 1B). Otherwise, the expression of miR-431 was significantly decreased in tumor tissues arising from patients suffered recurrence (P < 0.05, Fig. 1C). Taken together, reduced expression of miR-431 was associated with aggressive HCCs. Next, we found that miR-431 was obviously down-regulated in HCC cells compared with normal hepatic cells (P < 0.05, Fig. 1D). In addition, the expression of miR-431 in highly invasive HCC cell lines, MHCC97H and HCCLM3, were obviously lower than those in low invasive ones including SMMC-7721 and Hep3B (P < 0.05, Fig. 1D). These results demonstrate that reduced expression of miR-431 facilitates metastatic behavior of HCC cells.

Bottom Line: Herein, we found that miR-431 expression was reduced in HCC tissues compared to noncancerous tissues.We found that up-regulation of miR-431 expression decreased zinc finger E-box binding homeobox 1 (ZEB1) expression and inhibited the epithelial-mesenchymal transition (EMT) with increased E-cadherin expression and decreased vimentin expression in HCCLM3 cells.In conclusion, miR-431 inhibits migration and invasion of HCC cells by suppressing ZEB1-mediated EMT.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China.

ABSTRACT
MicroRNA-431 (miR-431) has been recognized as an oncogenic miRNA, being implicated in the initiation and development of human cancers. Recently, deregulation of miR-431 has been reported in several tumors. However, the clinical significance of miR-431 and its underlying role in human hepatocellular carcinoma (HCC) are poorly explored. Herein, we found that miR-431 expression was reduced in HCC tissues compared to noncancerous tissues. Otherwise, down-regulation of miR-431 was observed in aggressive tumor tissues. The levels of miR-431 expression in HCC cell lines were significantly lower than that in a nontransformed hepatic cell line. Clinical association analyses disclosed that a low level of miR-431 was prominently associated with poor prognostic features of HCC including venous infiltration, high Edmondson-Steiner grading and advanced tumor-node-metastasis (TNM) tumor stage. Our in vitro studies showed that up-regulation of miR-431 expression reduced cell invasion and migration in HCCLM3 cells. In contrast, down-regulation of miR-431 expression promoted SMMC-7721 cell invasion and migration. We found that up-regulation of miR-431 expression decreased zinc finger E-box binding homeobox 1 (ZEB1) expression and inhibited the epithelial-mesenchymal transition (EMT) with increased E-cadherin expression and decreased vimentin expression in HCCLM3 cells. Otherwise, down-regulation of miR-431 expression increased ZEB1 expression and promoted EMT in SMMC-7721 cells. Significantly, ZEB1 was identified as a target of miR-431 in HCC. ZEB1 knockdown abrogated the effect of miR-431 silencing on EMT and cell mobility in SMMC-7721 cells. In conclusion, miR-431 inhibits migration and invasion of HCC cells by suppressing ZEB1-mediated EMT.

No MeSH data available.


Related in: MedlinePlus