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Biomed Pharmacother. 2018 Sep;105:1133-1140. doi: 10.1016/j.biopha.2018.06.081. Epub 2018 Jun 21.

Long non-coding RNA HOTTIP is upregulated in renal cell carcinoma and regulates cell growth and apoptosis by epigenetically silencing of LATS2.

Author information

1
Department of Urology Surgery, Second Affiliated Hospital of Qiqihar Medical University, Heilongjiang Province, 161000, China.
2
Department of Urology Surgery, Second Affiliated Hospital of Qiqihar Medical University, Heilongjiang Province, 161000, China. Electronic address: ltaohlj@163.com.

Abstract

Renal cell carcinoma (RCC) is one of the most aggressive malignancies with increasing incidence worldwide and is characterized by dismal prognosis owing to a lack of early detection and prognostic biomarkers for this fatal disease. Accumulating studies demonstrated that abnormally expressed long non-coding RNAs (lncRNAs) are involved in tumorigenesis and progression. Specifically, HOTTIP is upregulated and exerts oncogenic properties in some cancers. However, its clinical significance, biological functions and molecular mechanisms in RCC have not been studied. In the current study, RT-qPCR was performed to quantify the relative expression of HOTTIP in RCC tissues and cells. Additionally, we explored its clinical value using Fisher's exact test. Moreover, cell growth and apoptosis altered by HOTTIP was evaluated in vitro and in vivo. Mechanistically, RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) analysis was used to determine its molecular mechanism in cell growth and apoptosis. As a result, upregulated HOTTIP is closely associated with unfavorable phenotypes in RCC patients. The mechanistic investigations showed that HOTTIP could bind to enhancer of zeste homolog 2 (EZH2) and lysine specific demethylase 1 (LSD1), thereby repressing LATS2 expression. Collectively, our study illustrates how HOTTIP plays an oncogenic role in RCC and may offer a potential therapeutic target for treating this fatal disease.

KEYWORDS:

HOTTIP; LATS2; Renal cell carcinoma; lncRNA

PMID:
30021349
DOI:
10.1016/j.biopha.2018.06.081
[Indexed for MEDLINE]

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