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TAp63 suppress metastasis via miR-133b in colon cancer cells.

Lin CW, Li XR, Zhang Y, Hu G, Guo YH, Zhou JY, Du J, Lv L, Gao K, Zhang Y, Deng H - Br. J. Cancer (2014)

Bottom Line: Furthermore, microRNA-133b is essential for the inhibitory effects of TAp63 on RhoA, E-cadherin and vimentin.Moreover, TAp63 inhibits cell migration and invasion through microRNA-133b.Correspondingly, the inhibitory effect of TAp63 on RhoA, E-cadherin, vimentin, migration and invasion can be blocked by the microRNA-133b inhibitor.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, People's Republic of China.

ABSTRACT

Background: TAp63 is a tumour-suppressor protein that is often underexpressed in various types of cancer. It has been shown to activate gene transcription depending on the transcription domain and to be closely related with metastasis. In this study, we demonstrate that TAp63 suppresses metastasis in colon cancer cells through microRNA-133b.

Methods: We evaluated the correlation of TAp63 and miR-133b with HT-29 and SW-620 cells and investigated the roles of TAp63 in the expression of RhoA, E-cadherin and vimentin. We further investigated the roles of TAp63-mediated invasion and migration of colon cancer cells.

Results: TAp63 expression is downregulated in colon cancer, and microRNA-133b is a transcriptional target of TAp63. Furthermore, microRNA-133b is essential for the inhibitory effects of TAp63 on RhoA, E-cadherin and vimentin. Moreover, TAp63 inhibits cell migration and invasion through microRNA-133b. Correspondingly, the inhibitory effect of TAp63 on RhoA, E-cadherin, vimentin, migration and invasion can be blocked by the microRNA-133b inhibitor.

Conclusions: TAp63 and microRNA-133b were able to suppress the metastasis of colon cancer. Both TAp63 and microRNA-133b may be potential biomarkers for diagnosis in colon cancer metastasis and may provide unique therapeutic targets for this common malignancy.

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Related in: MedlinePlus

TAp63 targets RhoA through miR-133b. HT-29 and SW-620 cells were either transfected with negative control (Neg Ctrl), TAp63 or miR-133b mimics or co-transfected with TAp63-expressing vector with miR-133b inhibitor (co-TF) for 72 h. (A) RhoA induction levels were detected by RT–PCR. (B) Percentage of RhoA mRNA is expressed relative to GAPDH. (C) Western blotting of RhoA levels in HT-29- and SW-620-transfected cells. (D) Percentage of RhoA protein is expressed relative to GAPDH. All data represent the means±s.d. of three different experiments analysed in triplicate. *P<0.05, #P>0.05.
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fig4: TAp63 targets RhoA through miR-133b. HT-29 and SW-620 cells were either transfected with negative control (Neg Ctrl), TAp63 or miR-133b mimics or co-transfected with TAp63-expressing vector with miR-133b inhibitor (co-TF) for 72 h. (A) RhoA induction levels were detected by RT–PCR. (B) Percentage of RhoA mRNA is expressed relative to GAPDH. (C) Western blotting of RhoA levels in HT-29- and SW-620-transfected cells. (D) Percentage of RhoA protein is expressed relative to GAPDH. All data represent the means±s.d. of three different experiments analysed in triplicate. *P<0.05, #P>0.05.

Mentions: To investigate whether this association was due to a functional relationship between TAp63 and miR-133b, we overexpressed TAp63 by transfecting HT-29 and SW-620 cells with vectors expressing TAp63 and measured the miR-133b expression levels. After the transfection, the expression of TAp63 was detected by RT–PCR and western blotting, which showed a significant increase in TAp63 expression (Figures 3A and B). This result was confirmed by qRT–PCR; HT-29 and SW-620 cells transfected with vectors expressing TAp63 induced a 132-fold increase in TAp63 mRNA expression (Figure 3C). Next, we detected the level of miR-133b by qRT–PCR. Figure 4D shows that the expression of miR-133b was induced roughly 18-fold by TAp63.


TAp63 suppress metastasis via miR-133b in colon cancer cells.

Lin CW, Li XR, Zhang Y, Hu G, Guo YH, Zhou JY, Du J, Lv L, Gao K, Zhang Y, Deng H - Br. J. Cancer (2014)

TAp63 targets RhoA through miR-133b. HT-29 and SW-620 cells were either transfected with negative control (Neg Ctrl), TAp63 or miR-133b mimics or co-transfected with TAp63-expressing vector with miR-133b inhibitor (co-TF) for 72 h. (A) RhoA induction levels were detected by RT–PCR. (B) Percentage of RhoA mRNA is expressed relative to GAPDH. (C) Western blotting of RhoA levels in HT-29- and SW-620-transfected cells. (D) Percentage of RhoA protein is expressed relative to GAPDH. All data represent the means±s.d. of three different experiments analysed in triplicate. *P<0.05, #P>0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4007221&req=5

fig4: TAp63 targets RhoA through miR-133b. HT-29 and SW-620 cells were either transfected with negative control (Neg Ctrl), TAp63 or miR-133b mimics or co-transfected with TAp63-expressing vector with miR-133b inhibitor (co-TF) for 72 h. (A) RhoA induction levels were detected by RT–PCR. (B) Percentage of RhoA mRNA is expressed relative to GAPDH. (C) Western blotting of RhoA levels in HT-29- and SW-620-transfected cells. (D) Percentage of RhoA protein is expressed relative to GAPDH. All data represent the means±s.d. of three different experiments analysed in triplicate. *P<0.05, #P>0.05.
Mentions: To investigate whether this association was due to a functional relationship between TAp63 and miR-133b, we overexpressed TAp63 by transfecting HT-29 and SW-620 cells with vectors expressing TAp63 and measured the miR-133b expression levels. After the transfection, the expression of TAp63 was detected by RT–PCR and western blotting, which showed a significant increase in TAp63 expression (Figures 3A and B). This result was confirmed by qRT–PCR; HT-29 and SW-620 cells transfected with vectors expressing TAp63 induced a 132-fold increase in TAp63 mRNA expression (Figure 3C). Next, we detected the level of miR-133b by qRT–PCR. Figure 4D shows that the expression of miR-133b was induced roughly 18-fold by TAp63.

Bottom Line: Furthermore, microRNA-133b is essential for the inhibitory effects of TAp63 on RhoA, E-cadherin and vimentin.Moreover, TAp63 inhibits cell migration and invasion through microRNA-133b.Correspondingly, the inhibitory effect of TAp63 on RhoA, E-cadherin, vimentin, migration and invasion can be blocked by the microRNA-133b inhibitor.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan 410013, People's Republic of China.

ABSTRACT

Background: TAp63 is a tumour-suppressor protein that is often underexpressed in various types of cancer. It has been shown to activate gene transcription depending on the transcription domain and to be closely related with metastasis. In this study, we demonstrate that TAp63 suppresses metastasis in colon cancer cells through microRNA-133b.

Methods: We evaluated the correlation of TAp63 and miR-133b with HT-29 and SW-620 cells and investigated the roles of TAp63 in the expression of RhoA, E-cadherin and vimentin. We further investigated the roles of TAp63-mediated invasion and migration of colon cancer cells.

Results: TAp63 expression is downregulated in colon cancer, and microRNA-133b is a transcriptional target of TAp63. Furthermore, microRNA-133b is essential for the inhibitory effects of TAp63 on RhoA, E-cadherin and vimentin. Moreover, TAp63 inhibits cell migration and invasion through microRNA-133b. Correspondingly, the inhibitory effect of TAp63 on RhoA, E-cadherin, vimentin, migration and invasion can be blocked by the microRNA-133b inhibitor.

Conclusions: TAp63 and microRNA-133b were able to suppress the metastasis of colon cancer. Both TAp63 and microRNA-133b may be potential biomarkers for diagnosis in colon cancer metastasis and may provide unique therapeutic targets for this common malignancy.

Show MeSH
Related in: MedlinePlus