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Interleukin 37 Expression Inhibits STAT3 to Suppress the Proliferation and Invasion of Human Cervical Cancer Cells.

Wang S, An W, Yao Y, Chen R, Zheng X, Yang W, Zhao Y, Hu X, Jiang E, Bie Y, Chen Z, Ouyang P, Zhang H, Xiong H - J Cancer (2015)

Bottom Line: Firstly, we found that IL-37 inhibited STAT3 expression at both mRNA and protein levels.Secondly, blockage of STAT3 using siRNAs reduced significantly the ability of IL-37 to suppress cell proliferation and invasion.This study demonstrated a new biological function of IL-37 and offered a potential molecule for CC treatment.

View Article: PubMed Central - PubMed

Affiliation: 1. Cancer Institute, Guangdong Medical University, Dongguan 523808, China;

ABSTRACT

Objectives: The most recently discovered cytokine interleukin 37 (IL-37) received growing attention. Its function on tumor is largely unknown. Here, we investigated the biological function of IL-37 on cervical cancer (CC). Materials and methods : HPV(+) Hela cells and HPV(-) C33A cells were used. RT-qPCR was performed to detect the transcription of IL-37, STAT3, TNF-αand IL-1β. Western blotting was used for protein detection. CCK-8 assay and transwell assay were employed for cell proliferation and invasion detection, respectively. Results : Successful gene transfection of IL-37 suppressed the proliferation and invasion of CC. Interestingly, IL-37 showed higher anticancer ability in HPV(+) Hela cells than that in HPV(-) C33A cells. Then, the molecular mechanism of IL-37 anticancer was explored. Firstly, we found that IL-37 inhibited STAT3 expression at both mRNA and protein levels. IL-37 also down regulated the phosphorylation of STAT3. Secondly, blockage of STAT3 using siRNAs reduced significantly the ability of IL-37 to suppress cell proliferation and invasion. Thirdly, STAT3 knockdown reduced markedly the inhibition of IL-37 on the transcription of tumor-derived TNF-α and IL-1β, indicating the contribution of STAT3 for the cancer associated antiinflammation of IL-37. Finally, STAT3 up regulation restored the ability of cell proliferation, cell invasion and the expression of inflammatory cytokines, TNF-α and IL-1β. Conclusions : IL-37 suppressed cell proliferation and invasion of CC and STAT3 is involved in this process. Thus, IL-37 emerges as a new anticancer cytokine for CC. This study demonstrated a new biological function of IL-37 and offered a potential molecule for CC treatment.

No MeSH data available.


Related in: MedlinePlus

STAT3 siRNA (siSTAT3) transfection reduced the anticancer ability of IL-37 in Hela and C33A cells. (A, B) SiSTAT3 suppressed the mRNA expression of STAT3 in Hela (A) and C33A (B) cells. (C, D) siSTAT3 suppressed the protein expression of STAT3 in Hela (C) and C33A (D) cells. (E, F) siSTAT3 and IL-37 transfection suppressed the cell proliferation of Hela (E) and C33A (F) cells. (G, H) siSTAT3 and IL-37 transfection suppressed the cell invasion of Hela (G) and C33A (H) cells. (I, J) STAT3 siRNA transfection reduced the anticancer ability of IL-37 to suppress cell proliferation of Hela (I) and C33A (J) cells. (K, L) STAT3 siRNA transfection reduced the anticancer ability of IL-37 to suppress cell invasion of Hela (K) and C33A (L) cells. NC: normal control. siSTAT3: STAT3 knockdown group. IL37-NC: IL-37 gene transfection group. IL37+siSTAT3: IL-37 gene transfection with blockage of STAT3 group.
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Figure 3: STAT3 siRNA (siSTAT3) transfection reduced the anticancer ability of IL-37 in Hela and C33A cells. (A, B) SiSTAT3 suppressed the mRNA expression of STAT3 in Hela (A) and C33A (B) cells. (C, D) siSTAT3 suppressed the protein expression of STAT3 in Hela (C) and C33A (D) cells. (E, F) siSTAT3 and IL-37 transfection suppressed the cell proliferation of Hela (E) and C33A (F) cells. (G, H) siSTAT3 and IL-37 transfection suppressed the cell invasion of Hela (G) and C33A (H) cells. (I, J) STAT3 siRNA transfection reduced the anticancer ability of IL-37 to suppress cell proliferation of Hela (I) and C33A (J) cells. (K, L) STAT3 siRNA transfection reduced the anticancer ability of IL-37 to suppress cell invasion of Hela (K) and C33A (L) cells. NC: normal control. siSTAT3: STAT3 knockdown group. IL37-NC: IL-37 gene transfection group. IL37+siSTAT3: IL-37 gene transfection with blockage of STAT3 group.

Mentions: siSTAT3 successfully knockdown STAT3 expression. The mRNA level of STAT3 was reduced by 85.1% in Hela cells (Figure 3A) and 79% in C33A cells (Figure 3B). The protein level of STAT3 was reduced by 55.6% in Hela cells (Figure 3C) and 61.98% in C33A cells (Figure 3D), respectively. Figure 3E and 3F showed that siSTAT3 and IL-37 gene transfection suppressed the cell proliferation. Figure 3G and 3H showed that siSTAT3 and IL-37 gene transfection suppressed the cell invasion.


Interleukin 37 Expression Inhibits STAT3 to Suppress the Proliferation and Invasion of Human Cervical Cancer Cells.

Wang S, An W, Yao Y, Chen R, Zheng X, Yang W, Zhao Y, Hu X, Jiang E, Bie Y, Chen Z, Ouyang P, Zhang H, Xiong H - J Cancer (2015)

STAT3 siRNA (siSTAT3) transfection reduced the anticancer ability of IL-37 in Hela and C33A cells. (A, B) SiSTAT3 suppressed the mRNA expression of STAT3 in Hela (A) and C33A (B) cells. (C, D) siSTAT3 suppressed the protein expression of STAT3 in Hela (C) and C33A (D) cells. (E, F) siSTAT3 and IL-37 transfection suppressed the cell proliferation of Hela (E) and C33A (F) cells. (G, H) siSTAT3 and IL-37 transfection suppressed the cell invasion of Hela (G) and C33A (H) cells. (I, J) STAT3 siRNA transfection reduced the anticancer ability of IL-37 to suppress cell proliferation of Hela (I) and C33A (J) cells. (K, L) STAT3 siRNA transfection reduced the anticancer ability of IL-37 to suppress cell invasion of Hela (K) and C33A (L) cells. NC: normal control. siSTAT3: STAT3 knockdown group. IL37-NC: IL-37 gene transfection group. IL37+siSTAT3: IL-37 gene transfection with blockage of STAT3 group.
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Related In: Results  -  Collection

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Figure 3: STAT3 siRNA (siSTAT3) transfection reduced the anticancer ability of IL-37 in Hela and C33A cells. (A, B) SiSTAT3 suppressed the mRNA expression of STAT3 in Hela (A) and C33A (B) cells. (C, D) siSTAT3 suppressed the protein expression of STAT3 in Hela (C) and C33A (D) cells. (E, F) siSTAT3 and IL-37 transfection suppressed the cell proliferation of Hela (E) and C33A (F) cells. (G, H) siSTAT3 and IL-37 transfection suppressed the cell invasion of Hela (G) and C33A (H) cells. (I, J) STAT3 siRNA transfection reduced the anticancer ability of IL-37 to suppress cell proliferation of Hela (I) and C33A (J) cells. (K, L) STAT3 siRNA transfection reduced the anticancer ability of IL-37 to suppress cell invasion of Hela (K) and C33A (L) cells. NC: normal control. siSTAT3: STAT3 knockdown group. IL37-NC: IL-37 gene transfection group. IL37+siSTAT3: IL-37 gene transfection with blockage of STAT3 group.
Mentions: siSTAT3 successfully knockdown STAT3 expression. The mRNA level of STAT3 was reduced by 85.1% in Hela cells (Figure 3A) and 79% in C33A cells (Figure 3B). The protein level of STAT3 was reduced by 55.6% in Hela cells (Figure 3C) and 61.98% in C33A cells (Figure 3D), respectively. Figure 3E and 3F showed that siSTAT3 and IL-37 gene transfection suppressed the cell proliferation. Figure 3G and 3H showed that siSTAT3 and IL-37 gene transfection suppressed the cell invasion.

Bottom Line: Firstly, we found that IL-37 inhibited STAT3 expression at both mRNA and protein levels.Secondly, blockage of STAT3 using siRNAs reduced significantly the ability of IL-37 to suppress cell proliferation and invasion.This study demonstrated a new biological function of IL-37 and offered a potential molecule for CC treatment.

View Article: PubMed Central - PubMed

Affiliation: 1. Cancer Institute, Guangdong Medical University, Dongguan 523808, China;

ABSTRACT

Objectives: The most recently discovered cytokine interleukin 37 (IL-37) received growing attention. Its function on tumor is largely unknown. Here, we investigated the biological function of IL-37 on cervical cancer (CC). Materials and methods : HPV(+) Hela cells and HPV(-) C33A cells were used. RT-qPCR was performed to detect the transcription of IL-37, STAT3, TNF-αand IL-1β. Western blotting was used for protein detection. CCK-8 assay and transwell assay were employed for cell proliferation and invasion detection, respectively. Results : Successful gene transfection of IL-37 suppressed the proliferation and invasion of CC. Interestingly, IL-37 showed higher anticancer ability in HPV(+) Hela cells than that in HPV(-) C33A cells. Then, the molecular mechanism of IL-37 anticancer was explored. Firstly, we found that IL-37 inhibited STAT3 expression at both mRNA and protein levels. IL-37 also down regulated the phosphorylation of STAT3. Secondly, blockage of STAT3 using siRNAs reduced significantly the ability of IL-37 to suppress cell proliferation and invasion. Thirdly, STAT3 knockdown reduced markedly the inhibition of IL-37 on the transcription of tumor-derived TNF-α and IL-1β, indicating the contribution of STAT3 for the cancer associated antiinflammation of IL-37. Finally, STAT3 up regulation restored the ability of cell proliferation, cell invasion and the expression of inflammatory cytokines, TNF-α and IL-1β. Conclusions : IL-37 suppressed cell proliferation and invasion of CC and STAT3 is involved in this process. Thus, IL-37 emerges as a new anticancer cytokine for CC. This study demonstrated a new biological function of IL-37 and offered a potential molecule for CC treatment.

No MeSH data available.


Related in: MedlinePlus