Estrogen receptor β promotes renal cell carcinoma progression via regulating LncRNA HOTAIR-miR-138/200c/204/217 associated CeRNA network

Abstract

Recent studies indicated that the estrogen receptor beta (ERβ) could affect the progression of prostate and bladder tumors, however, its roles in the renal cell carcinoma (RCC), remain to be elucidated. Here, we provide clinical evidence that ERβ expression is correlated in a negative manner with the overall survival/disease-free survival in RCC patients. Mechanism dissection revealed that targeting ERβ with ERβ-shRNA and stimulating the transactivation of ERβ with 17β-estradiol or environmental endocrine disrupting chemicals, all resulted in altering the lncRNA HOTAIR expression. The ERβ-modulated HOTAIR is able to function via antagonizing several microRNAs, including miR-138, miR-200c, miR-204, or miR-217 to impact various oncogenes, including ADAM9, CCND2, EZH2, VEGFA, VIM, ZEB1, and ZEB2, to promote RCC proliferation and invasion. Together, the identification of the ERβ-HOTAIR axis may provide us new biomarkers and/or therapeutic targets to better suppress RCC progression in the future.

Hotair mediates tumorigenesis through recruiting EZH2 in colorectal cancer

“…The elevated expression of Hotair was observed in multiple cancer types, [16][17][18] and our results also demonstrated that it was significantly upregulated in a panel of CRC cells ( Figure 1A). In 20 paired CRC clinical specimens, the expression of Hotair was increased in CRC tissues when compared with their adjacent nontumor tissues ( Figure 1B).…”

The emerging role of the long non-coding RNA HOTAIR in breast cancer development and treatment

“…Antagonizing behaviour of this lincRNA sponge the activity of miR-138/204/217 complex, among which miR-138/217 negatively regulate EZH2. This leads to upregulation of EZH2 and epigenetically promoter silencing of miR-200c downstream of HOTAIR, consequently directing malignant cells to proliferation and invasion [84]. Interestingly, ERβ could play crucial role in breast cancer cells progression, particularly EMT and metastasis [85].…”

Long non-coding RNA ARAP1-AS1 promotes the progression of bladder cancer by regulating miR-4735-3p/NOTCH2 axis

“…LncRNAs is well-known as endogenous competitively RNAs (ceRNA) in human cancers, thereby modulating their downstream gene expression. [16][17][18][19] Here, we explored whether ARAP1-AS1 can act as a ceRNA to regulate cellular processes in BCa. Mechanism experiments were designed and applied to detect the ceRNA pathway which centered with lncRNA ARAP1-AS1.…”