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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 are associated with malignant transformation and lower overall survival in CRC patients. (A) Expression of TLR2 in 39 pairs of tumour samples and matched adjacent noncancerous tissues was measured by real-time PCR. (B) Expression of TLR2 was determined by real-time PCR in 3 normal colon epithelial cells and 4 CRC cell lines (SW480, LS174T, SW620, and HCT116). (C) Expression of TLR2 was determined in 79 CRC tissues (grade1 n = 18; grade2 n = 20; grade3 n = 41) by real-time PCR. The statistical method analysed the correlation between the expression of TLR2 and tumour pathological grade. (D) Expression of TLR2 was checked in 79 CRC tissues (N0 n = 28; N1 n = 31; N2 n = 20) by real-time PCR. The statistical method analysed the correlation between the expression of TLR2 and tumour lymph node metastasis. (E) Lower overall survival of patients with high TLR2 levels (above median; n = 37) compared to patients with low TLR2 levels (below median; n = 42). (***p < 0.001; **p < 0.01; *p < 0.05).
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Figure 1: High TLR2 levels are associated with malignant transformation and lower overall survival in CRC patients. (A) Expression of TLR2 in 39 pairs of tumour samples and matched adjacent noncancerous tissues was measured by real-time PCR. (B) Expression of TLR2 was determined by real-time PCR in 3 normal colon epithelial cells and 4 CRC cell lines (SW480, LS174T, SW620, and HCT116). (C) Expression of TLR2 was determined in 79 CRC tissues (grade1 n = 18; grade2 n = 20; grade3 n = 41) by real-time PCR. The statistical method analysed the correlation between the expression of TLR2 and tumour pathological grade. (D) Expression of TLR2 was checked in 79 CRC tissues (N0 n = 28; N1 n = 31; N2 n = 20) by real-time PCR. The statistical method analysed the correlation between the expression of TLR2 and tumour lymph node metastasis. (E) Lower overall survival of patients with high TLR2 levels (above median; n = 37) compared to patients with low TLR2 levels (below median; n = 42). (***p < 0.001; **p < 0.01; *p < 0.05).

Mentions: To determine the potential roles of TLRs in the regulation of tumourigenesis, we first examined the expression of TLRs in CRC. Using real-time PCR and immunohistochemistry analysis, we analysed TLR2 expression in 39 paired samples (tumour and adjacent noncancerous tissues from the same patient) and found that TLR2 expression is significantly up-regulated in CRC tissues (Figure 1A and Additional file 1: Figure S1; ***p < 0.001). We observed that TLR2 expression was significantly up-regulated in 4 CRC cell lines compared with normal epithelial tissues (Figure 1B; ***p < 0.001). Additionally, we detected higher TLR2 expression in poorly differentiated tumour cells (SW620 and HCT116) compared with well-differentiated tumour cells (SW480 and LS174T). The TLR2 expression profile of human CRC tissues revealed that high levels of TLR2 correlated with more advanced pathology grades (1, 2, 3) and lymph node metastasis (N0, N1, N2) (Figures 1C and 1D; ***p < 0.001; **p < 0.01; *p < 0.05), suggesting an association between TLR2 expression and tumour progression. Accordingly, TLR2 levels above the median correlate with lower overall survival of patients with CRC (Figure 1E; p = 0.0025). The characteristics of the patients with colorectal carcinoma are listed in Table 1.


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 are associated with malignant transformation and lower overall survival in CRC patients. (A) Expression of TLR2 in 39 pairs of tumour samples and matched adjacent noncancerous tissues was measured by real-time PCR. (B) Expression of TLR2 was determined by real-time PCR in 3 normal colon epithelial cells and 4 CRC cell lines (SW480, LS174T, SW620, and HCT116). (C) Expression of TLR2 was determined in 79 CRC tissues (grade1 n = 18; grade2 n = 20; grade3 n = 41) by real-time PCR. The statistical method analysed the correlation between the expression of TLR2 and tumour pathological grade. (D) Expression of TLR2 was checked in 79 CRC tissues (N0 n = 28; N1 n = 31; N2 n = 20) by real-time PCR. The statistical method analysed the correlation between the expression of TLR2 and tumour lymph node metastasis. (E) Lower overall survival of patients with high TLR2 levels (above median; n = 37) compared to patients with low TLR2 levels (below median; n = 42). (***p < 0.001; **p < 0.01; *p < 0.05).
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Figure 1: High TLR2 levels are associated with malignant transformation and lower overall survival in CRC patients. (A) Expression of TLR2 in 39 pairs of tumour samples and matched adjacent noncancerous tissues was measured by real-time PCR. (B) Expression of TLR2 was determined by real-time PCR in 3 normal colon epithelial cells and 4 CRC cell lines (SW480, LS174T, SW620, and HCT116). (C) Expression of TLR2 was determined in 79 CRC tissues (grade1 n = 18; grade2 n = 20; grade3 n = 41) by real-time PCR. The statistical method analysed the correlation between the expression of TLR2 and tumour pathological grade. (D) Expression of TLR2 was checked in 79 CRC tissues (N0 n = 28; N1 n = 31; N2 n = 20) by real-time PCR. The statistical method analysed the correlation between the expression of TLR2 and tumour lymph node metastasis. (E) Lower overall survival of patients with high TLR2 levels (above median; n = 37) compared to patients with low TLR2 levels (below median; n = 42). (***p < 0.001; **p < 0.01; *p < 0.05).
Mentions: To determine the potential roles of TLRs in the regulation of tumourigenesis, we first examined the expression of TLRs in CRC. Using real-time PCR and immunohistochemistry analysis, we analysed TLR2 expression in 39 paired samples (tumour and adjacent noncancerous tissues from the same patient) and found that TLR2 expression is significantly up-regulated in CRC tissues (Figure 1A and Additional file 1: Figure S1; ***p < 0.001). We observed that TLR2 expression was significantly up-regulated in 4 CRC cell lines compared with normal epithelial tissues (Figure 1B; ***p < 0.001). Additionally, we detected higher TLR2 expression in poorly differentiated tumour cells (SW620 and HCT116) compared with well-differentiated tumour cells (SW480 and LS174T). The TLR2 expression profile of human CRC tissues revealed that high levels of TLR2 correlated with more advanced pathology grades (1, 2, 3) and lymph node metastasis (N0, N1, N2) (Figures 1C and 1D; ***p < 0.001; **p < 0.01; *p < 0.05), suggesting an association between TLR2 expression and tumour progression. Accordingly, TLR2 levels above the median correlate with lower overall survival of patients with CRC (Figure 1E; p = 0.0025). The characteristics of the patients with colorectal carcinoma are listed in Table 1.

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