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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

IL-37 is involved in different tumors. IL-37 has been found to play a role in three malignant tumors: fibrosarcoma, hepatocellular carcinoma and cervical cancer, by different molecular mechanisms. This figure showed three different mechanisms of IL-37 regulation on different tumors. FSC, fibrosarcoma; HCC, hepatocellular carcinoma; CC, Cervical Cancer.
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Figure 7: IL-37 is involved in different tumors. IL-37 has been found to play a role in three malignant tumors: fibrosarcoma, hepatocellular carcinoma and cervical cancer, by different molecular mechanisms. This figure showed three different mechanisms of IL-37 regulation on different tumors. FSC, fibrosarcoma; HCC, hepatocellular carcinoma; CC, Cervical Cancer.

Mentions: During the years, the relationship between IL-37 and tumors remain unclear. Our studies showed a role of IL-37 to inhibit the proliferation and invasion of CC cells, both HPV+ Hela and HPV- C33A. IL-37 has been reported to relate to fibrosarcoma 11 and HCC 12 in previous research (Figure 7). At first glance, it might seem haphazard for IL-37 exploration in the two very different tumors, both of the two studies discussed the mechanism via immune cells. By contrast, inflammations caused by HPV infection play very important role in cervical cancer. Thus, we detected IL-37 function on CC. IL-37 expression plasmid was transfected into Hela and C33A cells firstly. Once exogenous IL-37 was expressed, the proliferation and invasion of CC cells were inhibited significantly. These results demonstrated our guess. Interestingly, IL-37 showed stronger anticancer ability in HPV+ Hela cells than in HPV- C33A cells, in both proliferation and invasion aspects. The fact implied that this novel gene might have a unique role in virus infection. This might correlate with immune responses induced by HPV and needed further exploration.


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)

IL-37 is involved in different tumors. IL-37 has been found to play a role in three malignant tumors: fibrosarcoma, hepatocellular carcinoma and cervical cancer, by different molecular mechanisms. This figure showed three different mechanisms of IL-37 regulation on different tumors. FSC, fibrosarcoma; HCC, hepatocellular carcinoma; CC, Cervical Cancer.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4543756&req=5

Figure 7: IL-37 is involved in different tumors. IL-37 has been found to play a role in three malignant tumors: fibrosarcoma, hepatocellular carcinoma and cervical cancer, by different molecular mechanisms. This figure showed three different mechanisms of IL-37 regulation on different tumors. FSC, fibrosarcoma; HCC, hepatocellular carcinoma; CC, Cervical Cancer.
Mentions: During the years, the relationship between IL-37 and tumors remain unclear. Our studies showed a role of IL-37 to inhibit the proliferation and invasion of CC cells, both HPV+ Hela and HPV- C33A. IL-37 has been reported to relate to fibrosarcoma 11 and HCC 12 in previous research (Figure 7). At first glance, it might seem haphazard for IL-37 exploration in the two very different tumors, both of the two studies discussed the mechanism via immune cells. By contrast, inflammations caused by HPV infection play very important role in cervical cancer. Thus, we detected IL-37 function on CC. IL-37 expression plasmid was transfected into Hela and C33A cells firstly. Once exogenous IL-37 was expressed, the proliferation and invasion of CC cells were inhibited significantly. These results demonstrated our guess. Interestingly, IL-37 showed stronger anticancer ability in HPV+ Hela cells than in HPV- C33A cells, in both proliferation and invasion aspects. The fact implied that this novel gene might have a unique role in virus infection. This might correlate with immune responses induced by HPV and needed further exploration.

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