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Noncoding RNAs as sensors of tumor microenvironmental stress.

ABSTRACT: The tumor microenvironment (TME) has been demonstrated to modulate the biological behavior of tumors intensively. Multiple stress conditions are widely observed in the TME of many cancer types, such as hypoxia, inflammation, and nutrient deprivation. Recently, accumulating evidence demonstrates that the expression levels of noncoding RNAs (ncRNAs) are dramatically altered by TME stress, and the dysregulated ncRNAs can in turn regulate tumor cell proliferation, metastasis, and drug resistance. In this review, we elaborate on the signal transduction pathways or epigenetic pathways by which hypoxia-inducible factors (HIFs), inflammatory factors, and nutrient deprivation in TME regulate ncRNAs, and highlight the pivotal roles of TME stress-related ncRNAs in tumors. This helps to clarify the molecular regulatory networks between TME and ncRNAs, which may provide potential targets for cancer therapy.

SUBMITTER: Lv Y

PROVIDER: S-EPMC9288030 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Noncoding RNAs as sensors of tumor microenvironmental stress.

Lv Yue Y Lv Yinghao Y Wang Zhen Z Yuan Kefei K Zeng Yong Y

Journal of experimental & clinical cancer research : CR 20220716 1

The tumor microenvironment (TME) has been demonstrated to modulate the biological behavior of tumors intensively. Multiple stress conditions are widely observed in the TME of many cancer types, such as hypoxia, inflammation, and nutrient deprivation. Recently, accumulating evidence demonstrates that the expression levels of noncoding RNAs (ncRNAs) are dramatically altered by TME stress, and the dysregulated ncRNAs can in turn regulate tumor cell proliferation, metastasis, and drug resistance. In ...[more]

PMID: 35842651

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Project description:BackgroundThe landscape and biological functions of tumor suppressor long noncoding RNAs in breast cancer are still unknown.MethodsData from whole transcriptome sequencing of 33 breast specimens in the Harbin Medical University Cancer Center cohort and The Cancer Genome Atlas was applied to identify and validate the landscape of tumor suppressor long noncoding RNAs, which was further validated by The Cancer Genome Atlas pancancer data including 33 cancer types and 12,839 patients. Next, the expression model, prognostic roles, potential biological functions and epigenetic regulation of tumor suppressor long noncoding RNAs were investigated and validated in the breast cancer and pancancer cohorts. Finally, EPB41L4A-AS2 was selected to validate our novel finding, and the tumor suppressive roles of EPB41L4A-AS2 in breast cancer were examined.ResultsWe identified and validated the landscape of tumor suppressor long noncoding RNAs in breast cancer. The expression of the identified long noncoding RNAs was downregulated in cancer tissue samples compared with normal tissue samples, and these long noncoding RNAs correlated with a favorable prognosis in breast cancer patients and the patients in the pancancer cohort. Multiple carcinogenesis-associated biological functions were predicted to be regulated negatively by these long noncoding RNAs. Moreover, these long noncoding RNAs were transcriptionally regulated by epigenetic modification, including DNA methylation and histone methylation modification. Finally, EPB41L4A-AS2 inhibited breast cancer cell proliferation, migration and invasion and induced cell apoptosis in vitro. Mechanistically, EPB41L4A-AS2, acting at least in part as a tumor suppressor, upregulated tumor suppressor gene expression. Moreover, ZNF217 recruited EZH2 to the EPB41L4A-AS2 locus and suppressed the expression of EPB41L4A-AS2 by epigenetically increasing H3K27me3 enrichment.ConclusionsThis work enlarges the functional landscape of known long noncoding RNAs in human cancer and provides novel insights into the suppressive roles of these long noncoding RNAs.

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Noncoding RNAs as sensors of tumor microenvironmental stress.

Publications

Noncoding RNAs as sensors of tumor microenvironmental stress.

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