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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 inhibits cell invasion. Transwell invasion assays of HT-29 and SW-620 cells either transfected with negative control (Neg Ctrl), TAp63 or miR-133b mimics or co-transfected TAp63 expressing vector with miR-133b inhibitor (co-TF). After being transfected for 24 h, the cells were collected and seeded into the upper chamber. After 48 h, invasive cells were counted in five random high-power fields. All of the data represent the means±s.d. of three different experiments analysed in triplicate. *P<0.05, #P>0.05.
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fig7: TAp63 inhibits cell invasion. Transwell invasion assays of HT-29 and SW-620 cells either transfected with negative control (Neg Ctrl), TAp63 or miR-133b mimics or co-transfected TAp63 expressing vector with miR-133b inhibitor (co-TF). After being transfected for 24 h, the cells were collected and seeded into the upper chamber. After 48 h, invasive cells were counted in five random high-power fields. All of the data represent the means±s.d. of three different experiments analysed in triplicate. *P<0.05, #P>0.05.

Mentions: The repression of RhoA and its E-cadherin and vimentin targets suggests that TAp63 may have an important role in cell invasion and migration through miR-133b. To assess this, we performed transwell invasion assay and transwell migration assay. The transwell invasion assay was implemented to investigate the effect of TAp63 on the invasion of HT-29 and SW-620 cells. The transwell migration assay was implemented to investigate the effect of TAp63 on the migration of HT-29 and SW-620 cells. As shown in Figure 7, the invasion of HT-29 and SW-620 cells was restrained by overexpressing TAp63, compared with those transfected with the empty vector (*P<0.05). Similar results were obtained following the transfection of cells with miR-133b mimics. Conversely, cell invasion remained unchanged in cells co-transfecting the TAp63-expressing vector with the miR-133b inhibitor (#P>0.05). To further test the influence of TAp63 on cell migration, we performed a transwell migration assay. As shown in Figure 8, the migration of HT-29 and SW-620 cells was restrained by overexpressing TAp63, compared with those transfected with the empty vector (*P<0.05). Conversely, cell migration remained unchanged in cells co-transfecting the TAp63-expressing vector with the miR-133b inhibitor (#P>0.05).


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 inhibits cell invasion. Transwell invasion assays of HT-29 and SW-620 cells either transfected with negative control (Neg Ctrl), TAp63 or miR-133b mimics or co-transfected TAp63 expressing vector with miR-133b inhibitor (co-TF). After being transfected for 24 h, the cells were collected and seeded into the upper chamber. After 48 h, invasive cells were counted in five random high-power fields. All of the 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

fig7: TAp63 inhibits cell invasion. Transwell invasion assays of HT-29 and SW-620 cells either transfected with negative control (Neg Ctrl), TAp63 or miR-133b mimics or co-transfected TAp63 expressing vector with miR-133b inhibitor (co-TF). After being transfected for 24 h, the cells were collected and seeded into the upper chamber. After 48 h, invasive cells were counted in five random high-power fields. All of the data represent the means±s.d. of three different experiments analysed in triplicate. *P<0.05, #P>0.05.
Mentions: The repression of RhoA and its E-cadherin and vimentin targets suggests that TAp63 may have an important role in cell invasion and migration through miR-133b. To assess this, we performed transwell invasion assay and transwell migration assay. The transwell invasion assay was implemented to investigate the effect of TAp63 on the invasion of HT-29 and SW-620 cells. The transwell migration assay was implemented to investigate the effect of TAp63 on the migration of HT-29 and SW-620 cells. As shown in Figure 7, the invasion of HT-29 and SW-620 cells was restrained by overexpressing TAp63, compared with those transfected with the empty vector (*P<0.05). Similar results were obtained following the transfection of cells with miR-133b mimics. Conversely, cell invasion remained unchanged in cells co-transfecting the TAp63-expressing vector with the miR-133b inhibitor (#P>0.05). To further test the influence of TAp63 on cell migration, we performed a transwell migration assay. As shown in Figure 8, the migration of HT-29 and SW-620 cells was restrained by overexpressing TAp63, compared with those transfected with the empty vector (*P<0.05). Conversely, cell migration remained unchanged in cells co-transfecting the TAp63-expressing vector with the miR-133b inhibitor (#P>0.05).

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