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Merck
  • LncRNA TINCR favors tumorigenesis via STAT3-TINCR-EGFR-feedback loop by recruiting DNMT1 and acting as a competing endogenous RNA in human breast cancer.

LncRNA TINCR favors tumorigenesis via STAT3-TINCR-EGFR-feedback loop by recruiting DNMT1 and acting as a competing endogenous RNA in human breast cancer.

Cell death & disease (2021-01-16)
Qin Wang, Jiena Liu, Zilong You, Yanling Yin, Lei Liu, Yujuan Kang, Siwei Li, Shipeng Ning, Hui Li, Yajie Gong, Shouping Xu, Da Pang
摘要

The long noncoding RNA (lncRNA) TINCR has recently been found to be associated with the progression of human malignancies, but the molecular mechanism of TINCR action remains elusive, particularly in breast cancer. The oncogenic role of TINCR was examined in vitro and in vivo in breast cancer. Next, the interaction between TINCR, DNMT1, and miR-503-5p methylation was explored. Moreover, the mechanism by which TINCR enhances EGFR expression and downstream signaling via an RNA-RNA interaction was comprehensively investigated. Furthermore, upstream transcriptional regulation of TINCR expression by STAT3 was examined by performing chromatin immunoprecipitation. Finally, feedback signaling in the STAT3-TINCR-EGFR downstream cascade was also investigated. TINCR is upregulated in human breast cancer tissues, and TINCR knockdown suppresses tumorigenesis in vitro and in vivo. Mechanistically, TINCR recruits DNMT1 to the miR-503-5p locus promoter, which increases the methylation and suppresses the transcriptional expression of miR-503-5p. Furthermore, TINCR also functions as a competing endogenous RNA to upregulate EGFR expression by sponging miR-503-5p. In addition, TINCR stimulates JAK2-STAT3 signaling downstream from EGFR, and STAT3 reciprocally enhances the transcriptional expression of TINCR. Our findings broaden the current understanding of the diverse manners in which TINCR functions in cancer biology. The newly identified STAT3-TINCR-EGFR-feedback loop could serve as a potential therapeutic target for human cancer.

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海美溴铵, ≥95%
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BRAND®内嵌小室 - 单个,13mm,适用于24/6孔BRANDplates®, smooth-walled, PC membrane, pore size 0.4 μm
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Crystal Violet lactone, Dye content 97 %
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