Dataset Information

Long non-coding RNA HOTTIP enhances IL-6 expression to potentiate immune escape of ovarian cancer cells by upregulating the expression of PD-L1 in neutrophils.

ABSTRACT:

Background

Long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP), has been demonstrated to be a vital biomarker when evaluating the prognosis of multiple cancers. Nevertheless, the potential function of HOTTIP in ovarian cancer (OC), a prevalent cancer among women worldwide, remains elusive. Hence, the current study aimed to elucidate the functional relevance of HOTTIP in the development of OC.

Methods

Positive expression of PD-L1 and IL-6 was determined using immunohistochemical staining in the collected OC and normal tissues. The correlation of IL-6 and PD-L1 was analyzed using flow cytometry, Western blot analysis as well as Pearson's correlation coefficient. The interaction among HOTTIP, c-jun and IL-6 was investigated with the use of RIP, ChIP and dual luciferase reporter gene assays. Finally, the effects of HOTTIP on T cell proliferation and infiltration were identified through gain- and loss-of-function studies in vitro and in vivo.

Results

HOTTIP, IL-6 and PD-L1 were all highly expressed in OC tissues. A positive correlation was observed between IL-6 and PD-L1 and that between HOTTIP and IL-6 in OC tissues. HOTTIP was noted to promote the expression of IL-6 by binding to c-jun, which resulted in a promoted PD-L1 expression in neutrophils and immune escape while inhibiting T cell proliferation as well as tumor immunotherapy.

Conclusion

Taken together, our study unveiled that HOTTIP could promote the secretion of IL-6, and consequently up-regulate the expression of PD-L1 in neutrophils, thus inhibiting the activity of T cells and ultimately accelerating immune escape of OC cells. Our study provides a potential therapeutic strategy by targeting HOTTIP in OC.

SUBMITTER: Shang A

PROVIDER: S-EPMC6751824 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

Long non-coding RNA HOTTIP enhances IL-6 expression to potentiate immune escape of ovarian cancer cells by upregulating the expression of PD-L1 in neutrophils.

Shang Anquan A Wang Weiwei W Gu Chenzheng C Chen Chen C Zeng Bingjie B Yang Yibao Y Ji Ping P Sun Junjun J Wu Junlu J Lu Wenying W Sun Zujun Z Li Dong D

Journal of experimental & clinical cancer research : CR 20190918 1

<h4>Background</h4>Long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP), has been demonstrated to be a vital biomarker when evaluating the prognosis of multiple cancers. Nevertheless, the potential function of HOTTIP in ovarian cancer (OC), a prevalent cancer among women worldwide, remains elusive. Hence, the current study aimed to elucidate the functional relevance of HOTTIP in the development of OC.<h4>Methods</h4>Positive expression of PD-L1 and IL-6 was determined using im ...[more]

PMID: 31533774

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Dataset Information

Long non-coding RNA HOTTIP enhances IL-6 expression to potentiate immune escape of ovarian cancer cells by upregulating the expression of PD-L1 in neutrophils.

Background

Methods

Results

Conclusion

Publications

Long non-coding RNA HOTTIP enhances IL-6 expression to potentiate immune escape of ovarian cancer cells by upregulating the expression of PD-L1 in neutrophils.

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