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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 inhibition ability of IL-37 on TNF-αand IL-1βin Hela and C33A cells. (A, B) siSTAT3 reduced the inhibition ability of IL-37 on TNF-αtranscription in Hela cells (A) and in C33A cells (B). (C, D) siSTAT3 reduced the inhibition ability of IL-37 onIL-1βtranscription in Hela cells (C) and in C33A cells (D). 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 4: STAT3 siRNA (siSTAT3) transfection reduced the inhibition ability of IL-37 on TNF-αand IL-1βin Hela and C33A cells. (A, B) siSTAT3 reduced the inhibition ability of IL-37 on TNF-αtranscription in Hela cells (A) and in C33A cells (B). (C, D) siSTAT3 reduced the inhibition ability of IL-37 onIL-1βtranscription in Hela cells (C) and in C33A cells (D). 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 suppressed the inhibition ability of IL-37 on the transcription of TNF-αand IL-1β. STAT3 is known as a novel transcription factor for many downstream molecules. Here, we detected whether IL-37 influences TNF-αand IL-1βtranscription activity through STAT3. Here, the gene transcription level is relative to GAPDH. Under the state of STAT3 knockdown, compared IL37-NC group to IL37+siSTAT3 group, the transcription level of TNF-αwas reduced from 0.46 to 0.29 (48h) in Hela cells(Figure 4A) and from 0.521 to 0.25 in C33A cells (Figure 4B). The transcription level of IL-1βwas reduced from 0.35 to 0.24 (48h) in Hela cells (Figure 4C) and from 0.51 to 0.35 in C33A cells (Figure 4D). These results suggested that STAT3 contributed to the regulation of IL-37 on TNF-αand IL-1β.


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 inhibition ability of IL-37 on TNF-αand IL-1βin Hela and C33A cells. (A, B) siSTAT3 reduced the inhibition ability of IL-37 on TNF-αtranscription in Hela cells (A) and in C33A cells (B). (C, D) siSTAT3 reduced the inhibition ability of IL-37 onIL-1βtranscription in Hela cells (C) and in C33A cells (D). 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 4: STAT3 siRNA (siSTAT3) transfection reduced the inhibition ability of IL-37 on TNF-αand IL-1βin Hela and C33A cells. (A, B) siSTAT3 reduced the inhibition ability of IL-37 on TNF-αtranscription in Hela cells (A) and in C33A cells (B). (C, D) siSTAT3 reduced the inhibition ability of IL-37 onIL-1βtranscription in Hela cells (C) and in C33A cells (D). 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 suppressed the inhibition ability of IL-37 on the transcription of TNF-αand IL-1β. STAT3 is known as a novel transcription factor for many downstream molecules. Here, we detected whether IL-37 influences TNF-αand IL-1βtranscription activity through STAT3. Here, the gene transcription level is relative to GAPDH. Under the state of STAT3 knockdown, compared IL37-NC group to IL37+siSTAT3 group, the transcription level of TNF-αwas reduced from 0.46 to 0.29 (48h) in Hela cells(Figure 4A) and from 0.521 to 0.25 in C33A cells (Figure 4B). The transcription level of IL-1βwas reduced from 0.35 to 0.24 (48h) in Hela cells (Figure 4C) and from 0.51 to 0.35 in C33A cells (Figure 4D). These results suggested that STAT3 contributed to the regulation of IL-37 on TNF-αand IL-1β.

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