Limits...
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

MiR-431 reduces migration and invasion of HCC cells. (A) HCCLM3 cells that were transfected with miR-control (control) and miR-431, respectively, were subjected to qRT-PCR for miR-431 expression. Quantitative analysis indicated that miR-431 was significantly up-regulated by miR-431 expression vectors in HCCLM3. n = 6, ∗P < 0.05. (B) Cell migration as measured by Boyden chamber assays was inhibited by up-regulation of miR-431 in HCCLM3 cells as compared with control cells. MiR-431 overexpressing HCCLM3 cells conferred a less number of invaded cells as compared with control cells. n = 3 repeats with similar results, ∗P < 0.05. (C) SMMC-7721 cells that were transfected with negative control (NC) and miR-431 inhibiotr (anti-miR-431), respectively, were subjected to qRT-PCR for miR-431 expression. n = 6, ∗P < 0.05. (D) Down-regulation of miR-431 promoted cell migration and invasion in SMMC-7721 cells. n = 3 repeats with similar results, ∗P < 0.05.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4664716&req=5

f0010: MiR-431 reduces migration and invasion of HCC cells. (A) HCCLM3 cells that were transfected with miR-control (control) and miR-431, respectively, were subjected to qRT-PCR for miR-431 expression. Quantitative analysis indicated that miR-431 was significantly up-regulated by miR-431 expression vectors in HCCLM3. n = 6, ∗P < 0.05. (B) Cell migration as measured by Boyden chamber assays was inhibited by up-regulation of miR-431 in HCCLM3 cells as compared with control cells. MiR-431 overexpressing HCCLM3 cells conferred a less number of invaded cells as compared with control cells. n = 3 repeats with similar results, ∗P < 0.05. (C) SMMC-7721 cells that were transfected with negative control (NC) and miR-431 inhibiotr (anti-miR-431), respectively, were subjected to qRT-PCR for miR-431 expression. n = 6, ∗P < 0.05. (D) Down-regulation of miR-431 promoted cell migration and invasion in SMMC-7721 cells. n = 3 repeats with similar results, ∗P < 0.05.

Mentions: We transduced HCC cell line, HCCLM3, with miR-431 expression vector and the control vector for miR-431. The expression of miR-431 was obviously overexpressed by miR-431 expression vector in HCCLM3 cells as assessed by qRT-PCR (P < 0.05, Fig. 2A). Cell migration tested by Boyden chamber assays showed that overexpression of miR-431 led to a significant reduction of migrated cell numbers in HCCLM3 cells (P < 0.05, Fig. 2B). Otherwise, Transwell assays indicated that the number of invaded HCCLM3 cells was obviously decreased after overexpression of miR-431 (P < 0.05, Fig. 2B). Next, miR-431 down-regulating SMMC-7721 cells was established and measured by qRT-PCR (P < 0.05, Fig. 2C). On the contrary, knockdown of miR-431 evidently promoted migration and invasion of SMMC-7721 cells (P < 0.05, respectively, Fig. 2D). However, MTT assays indicated that the cell viability was not significantly changed after manipulating miR-431 expression levels in both HCCLM3 and SMMC-7721 cells (P > 0.05, respectively, Fig. S1). Taken together, miR-431 inhibits migration and invasion 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)

MiR-431 reduces migration and invasion of HCC cells. (A) HCCLM3 cells that were transfected with miR-control (control) and miR-431, respectively, were subjected to qRT-PCR for miR-431 expression. Quantitative analysis indicated that miR-431 was significantly up-regulated by miR-431 expression vectors in HCCLM3. n = 6, ∗P < 0.05. (B) Cell migration as measured by Boyden chamber assays was inhibited by up-regulation of miR-431 in HCCLM3 cells as compared with control cells. MiR-431 overexpressing HCCLM3 cells conferred a less number of invaded cells as compared with control cells. n = 3 repeats with similar results, ∗P < 0.05. (C) SMMC-7721 cells that were transfected with negative control (NC) and miR-431 inhibiotr (anti-miR-431), respectively, were subjected to qRT-PCR for miR-431 expression. n = 6, ∗P < 0.05. (D) Down-regulation of miR-431 promoted cell migration and invasion in SMMC-7721 cells. n = 3 repeats with similar results, ∗P < 0.05.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0010: MiR-431 reduces migration and invasion of HCC cells. (A) HCCLM3 cells that were transfected with miR-control (control) and miR-431, respectively, were subjected to qRT-PCR for miR-431 expression. Quantitative analysis indicated that miR-431 was significantly up-regulated by miR-431 expression vectors in HCCLM3. n = 6, ∗P < 0.05. (B) Cell migration as measured by Boyden chamber assays was inhibited by up-regulation of miR-431 in HCCLM3 cells as compared with control cells. MiR-431 overexpressing HCCLM3 cells conferred a less number of invaded cells as compared with control cells. n = 3 repeats with similar results, ∗P < 0.05. (C) SMMC-7721 cells that were transfected with negative control (NC) and miR-431 inhibiotr (anti-miR-431), respectively, were subjected to qRT-PCR for miR-431 expression. n = 6, ∗P < 0.05. (D) Down-regulation of miR-431 promoted cell migration and invasion in SMMC-7721 cells. n = 3 repeats with similar results, ∗P < 0.05.
Mentions: We transduced HCC cell line, HCCLM3, with miR-431 expression vector and the control vector for miR-431. The expression of miR-431 was obviously overexpressed by miR-431 expression vector in HCCLM3 cells as assessed by qRT-PCR (P < 0.05, Fig. 2A). Cell migration tested by Boyden chamber assays showed that overexpression of miR-431 led to a significant reduction of migrated cell numbers in HCCLM3 cells (P < 0.05, Fig. 2B). Otherwise, Transwell assays indicated that the number of invaded HCCLM3 cells was obviously decreased after overexpression of miR-431 (P < 0.05, Fig. 2B). Next, miR-431 down-regulating SMMC-7721 cells was established and measured by qRT-PCR (P < 0.05, Fig. 2C). On the contrary, knockdown of miR-431 evidently promoted migration and invasion of SMMC-7721 cells (P < 0.05, respectively, Fig. 2D). However, MTT assays indicated that the cell viability was not significantly changed after manipulating miR-431 expression levels in both HCCLM3 and SMMC-7721 cells (P > 0.05, respectively, Fig. S1). Taken together, miR-431 inhibits migration and invasion 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