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The regulation of Toll-like receptor 2 by miR-143 suppresses the invasion and migration of a subset of human colorectal carcinoma cells.

Guo H, Chen Y, Hu X, Qian G, Ge S, Zhang J - Mol. Cancer (2013)

Bottom Line: We also found that miR-143, a putative tumour suppressor that is down-regulated in CRC tissues, reduces the invasion and migration of CRC cells primarily via TLR2.Utilising a xenograft mouse model, we demonstrated that re-expression of miR-143 inhibits CRC cell colonisation in vivo. miR-143 blocks the TLR2 signalling pathway in human CRC cells.This knowledge may pave the way for new clinical applications utilising miR-143 mimics in the treatment of patients with CRC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Laboratory, Shanghai Third People's Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai 200019, PR China. sxguohaiyan@126.com

ABSTRACT

Background: The Toll-like receptor 2 (TLR2)-driven tissue response may promote neoangiogenesis and tumour growth by mechanisms that are poorly understood.

Methods: We investigated the expression levels of TLR2 and associated-miRNAs in colorectal carcinoma (CRC) tissues and cell lines using real-time PCR, northern blotting and western blotting. Survival curver was generated by Log-Rank test and the role of TLR2 signalling in tumour invasion and migration was determined by transwell analysis kits.

Results: We observed that the tissues from CRC patients express relatively high levels of TLR2. Targeting TLR2 markedly reduces the invasion and migration of CRC cells. We also found that miR-143, a putative tumour suppressor that is down-regulated in CRC tissues, reduces the invasion and migration of CRC cells primarily via TLR2. Utilising a xenograft mouse model, we demonstrated that re-expression of miR-143 inhibits CRC cell colonisation in vivo.

Conclusion: miR-143 blocks the TLR2 signalling pathway in human CRC cells. This knowledge may pave the way for new clinical applications utilising miR-143 mimics in the treatment of patients with CRC.

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Related in: MedlinePlus

High TLR2 levels facilitate CRC cell migration and invasion. (A) Expression of TLR2 was measured in SW620 and HCT116 cells treated with siRNA for TLR2 (siTLR2). (B) Proliferation was detected using a Cell Counting Kit-8 in SW620 and HCT116 cells treated with siTLR2. (C) Migration of SW620 and HCT116 cells treated with siTLR2 was determined using Transwell chambers untreated with matrigel. (D) Invasion of SW620 and HCT116 cells treated with siTLR2 was determined using matrigel-treated Transwell chambers. (**p < 0.01; *p < 0.05).
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Figure 2: High TLR2 levels facilitate CRC cell migration and invasion. (A) Expression of TLR2 was measured in SW620 and HCT116 cells treated with siRNA for TLR2 (siTLR2). (B) Proliferation was detected using a Cell Counting Kit-8 in SW620 and HCT116 cells treated with siTLR2. (C) Migration of SW620 and HCT116 cells treated with siTLR2 was determined using Transwell chambers untreated with matrigel. (D) Invasion of SW620 and HCT116 cells treated with siTLR2 was determined using matrigel-treated Transwell chambers. (**p < 0.01; *p < 0.05).

Mentions: We examined the role of TLR2 in CRC cell invasion, migration, and growth. To examine the down-regulating effect of siRNA on TLR2 expression, we performed a qRT-PCR analysis (Figure 2A and Additional file 2: Figure S2A; left panel) and a western blot analysis (Figure 2A and Additional file 2: Figure S2B; right panel) 48 h after transfecting SW620 and HCT116 cells with siRNA for TLR2 (siTLR2). As shown in Figure 2A, compared to the negative control group (siRNA-NC), ectopic expression of siTLR2 significantly decreased the expression of TLR2.


The regulation of Toll-like receptor 2 by miR-143 suppresses the invasion and migration of a subset of human colorectal carcinoma cells.

Guo H, Chen Y, Hu X, Qian G, Ge S, Zhang J - Mol. Cancer (2013)

High TLR2 levels facilitate CRC cell migration and invasion. (A) Expression of TLR2 was measured in SW620 and HCT116 cells treated with siRNA for TLR2 (siTLR2). (B) Proliferation was detected using a Cell Counting Kit-8 in SW620 and HCT116 cells treated with siTLR2. (C) Migration of SW620 and HCT116 cells treated with siTLR2 was determined using Transwell chambers untreated with matrigel. (D) Invasion of SW620 and HCT116 cells treated with siTLR2 was determined using matrigel-treated Transwell chambers. (**p < 0.01; *p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750391&req=5

Figure 2: High TLR2 levels facilitate CRC cell migration and invasion. (A) Expression of TLR2 was measured in SW620 and HCT116 cells treated with siRNA for TLR2 (siTLR2). (B) Proliferation was detected using a Cell Counting Kit-8 in SW620 and HCT116 cells treated with siTLR2. (C) Migration of SW620 and HCT116 cells treated with siTLR2 was determined using Transwell chambers untreated with matrigel. (D) Invasion of SW620 and HCT116 cells treated with siTLR2 was determined using matrigel-treated Transwell chambers. (**p < 0.01; *p < 0.05).
Mentions: We examined the role of TLR2 in CRC cell invasion, migration, and growth. To examine the down-regulating effect of siRNA on TLR2 expression, we performed a qRT-PCR analysis (Figure 2A and Additional file 2: Figure S2A; left panel) and a western blot analysis (Figure 2A and Additional file 2: Figure S2B; right panel) 48 h after transfecting SW620 and HCT116 cells with siRNA for TLR2 (siTLR2). As shown in Figure 2A, compared to the negative control group (siRNA-NC), ectopic expression of siTLR2 significantly decreased the expression of TLR2.

Bottom Line: We also found that miR-143, a putative tumour suppressor that is down-regulated in CRC tissues, reduces the invasion and migration of CRC cells primarily via TLR2.Utilising a xenograft mouse model, we demonstrated that re-expression of miR-143 inhibits CRC cell colonisation in vivo. miR-143 blocks the TLR2 signalling pathway in human CRC cells.This knowledge may pave the way for new clinical applications utilising miR-143 mimics in the treatment of patients with CRC.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Laboratory, Shanghai Third People's Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai 200019, PR China. sxguohaiyan@126.com

ABSTRACT

Background: The Toll-like receptor 2 (TLR2)-driven tissue response may promote neoangiogenesis and tumour growth by mechanisms that are poorly understood.

Methods: We investigated the expression levels of TLR2 and associated-miRNAs in colorectal carcinoma (CRC) tissues and cell lines using real-time PCR, northern blotting and western blotting. Survival curver was generated by Log-Rank test and the role of TLR2 signalling in tumour invasion and migration was determined by transwell analysis kits.

Results: We observed that the tissues from CRC patients express relatively high levels of TLR2. Targeting TLR2 markedly reduces the invasion and migration of CRC cells. We also found that miR-143, a putative tumour suppressor that is down-regulated in CRC tissues, reduces the invasion and migration of CRC cells primarily via TLR2. Utilising a xenograft mouse model, we demonstrated that re-expression of miR-143 inhibits CRC cell colonisation in vivo.

Conclusion: miR-143 blocks the TLR2 signalling pathway in human CRC cells. This knowledge may pave the way for new clinical applications utilising miR-143 mimics in the treatment of patients with CRC.

Show MeSH
Related in: MedlinePlus