HOTAIR-mediated reciprocal regulation of EZH2 and DNMT1 contribute to polyphyllin I-inhibited growth of castration-resistant prostate cancer cells in vitro and in vivo

Xiang, Shulin; Zou, PeiLiang; Tang, Qing; Zheng, Fang; Wu, Jingjing; Chen, Zhiqiang; Hann, Swei Sunny

doi:10.1016/j.bbagen.2017.12.001

Cited by 48 publications

(39 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, EZH2 may also recruit DNMT1 to the promoter region of its target genes. DNMTs and methyl-CpG binding protein 2 were reported to play an important role in methylation modification (35)(36)(37). These studies raise the possibility that lncRNAs may have a primary role in recruiting polycomb proteins to their target genes (32,36).…”

Section: Discussionmentioning

confidence: 97%

Long Non-coding RNA LINC00114 Facilitates Colorectal Cancer Development Through EZH2/DNMT1-Induced miR-133b Suppression

Chen

et al. 2019

Front. Oncol.

View full text Add to dashboard Cite

This study aimed to identify the roles of the long non-coding RNA LINC00114 in colorectal cancer (CRC) development. The expression levels of LINC00114 and miR-133b in CRC were determined by reverse transcription (RT)-polymerase chain reaction (PCR) and the functions of LINC00114 in CRC were evaluated in vitro and in vivo. Methylationspecific PCR assay was performed to detect the miR-133b promoter methylation in CRC cells. Bioinformatics analysis, RNA immunoprecipitation, dual luciferase assay, RNA pull-down, co-immunoprecipitation (IP), and chromatin IP (ChIP) assays were used to elucidate whether LINC00114 could recruit EZH2/DNMT1 and bind to the miR-133b promoter region, leading to dysregulated methylation and the depression of miR-133b. The expression levels of DNA methyltransferases (DNMTs), EZH2, and nucleoporin 214(NUP214) were analyzed by western blotting. Data showed that LINC00114 was highly expressed, whereas miR-133b was downregulated in the CRC tissues and cells. In vitro, silencing LINC00114 inhibited cell proliferation and impeded cell cycle at the G1/S phase by upregulating miR-133b. In vivo, LINC00114 knockdown reduced tumor growth. Further analysis showed that the methylation in miR-133b promoter region was increased in the CRC and silencing LINC00114 increased miR-133b expression through depressing methylation of its promoter region. ChIP-PCR experiments demonstrated that EZH2 and DNMT1 could bind to the miR-133b promoter region and it was abolished by LINC00114 knockdown. sh-EZH2 reversed the overexpression of DNMTs and CRC cell cycle progression induced by the LINC00114 upregulation. LINC00114 could regulate the NUP214 protein expression by sponging miR-133b. These results demonstrated that LINC00114 suppressed miR-133b expression via EZH2/DNMT1-mediated methylation of its promoter region, indicating that LINC00114 might be a potential novel target for CRC diagnosis and treatment.

show abstract

Section: Discussionmentioning

confidence: 97%

Long Non-coding RNA LINC00114 Facilitates Colorectal Cancer Development Through EZH2/DNMT1-Induced miR-133b Suppression

Chen

et al. 2019

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…We recently observed that PPI inhibited the growth of CRPC cells by inhibiting HOTAIR expression, thereby repressing EZH2 and DNMT1. This result revealed a novel mechanism for HOTAIR-mediated regulation of DNMT1 and EZH2 in response to PPI in inhibiting the growth of CRPC cells [59]. Interestingly, one study demonstrated the association of HOTAIR polymorphisms and genetic variants with PCa.…”

Section: Hotair In Prostate Cancermentioning

confidence: 98%

HOTAIR: An Oncogenic Long Non-Coding RNA in Human Cancer

Tang

Hann

2018

Cell Physiol Biochem

Self Cite

204

127

View full text Add to dashboard Cite

Long non-coding RNAs (LncRNAs) represent a novel class of noncoding RNAs that are longer than 200 nucleotides without protein-coding potential and function as novel master regulators in various human diseases, including cancer. Accumulating evidence shows that lncRNAs are dysregulated and implicated in various aspects of cellular homeostasis, such as proliferation, apoptosis, mobility, invasion, metastasis, chromatin remodeling, gene transcription, and post-transcriptional processing. However, the mechanisms by which lncRNAs regulate various biological functions in human diseases have yet to be determined. HOX antisense intergenic RNA (HOTAIR) is a recently discovered lncRNA and plays a critical role in various areas of cancer, such as proliferation, survival, migration, drug resistance, and genomic stability. In this review, we briefly introduce the concept, identification, and biological functions of HOTAIR. We then describe the involvement of HOTAIR that has been associated with tumorigenesis, growth, invasion, cancer stem cell differentiation, metastasis, and drug resistance in cancer. We also discuss emerging insights into the role of HOTAIR as potential biomarkers and therapeutic targets for novel treatment paradigms in cancer.

show abstract

“…Studies have demonstrated the important roles of lncRNAs such as HOTAIR in growth and progression of cancers . Herein, the results unveiled that SM significantly inhibited the expression as well as the promoter activity of HOTAIR (Figure C,D).…”

Section: Resultsmentioning

confidence: 73%

“…This further confirmed the inhibitory effect of SM on the growth of NSCLC cells. Moreover, SM induced a high magnitude of apoptosis, as determined by staining with Annexin V/ PI and flow cytometry analysis (Figure 1B).Studies have demonstrated the important roles of lncRNAssuch as HOTAIR in growth and progression of cancers 13,36. Herein, the results unveiled that SM significantly inhibited the expression as well as the promoter activity of HOTAIR (Figure 1C,D).Moreover, siRNA mediated silencing HOTAIR significantly inhibited the growth and invasion of A549 and PC9 cells as determined by MTT and in vitro invasion assays (Figure 1E,F), respectively.Overexpression of HOTAIR, on the other hand, diminished the inhibitory effect of SM on cell growth (Figure 1G).…”

mentioning

confidence: 93%

Novel reciprocal interaction of lncRNA HOTAIR and miR‐214‐3p contribute to the solamargine‐inhibited PDPK1 gene expression in human lung cancer

Tang

Zheng

Liu

et al. 2019

J Cellular Molecular Medi

Self Cite

View full text Add to dashboard Cite

Solamargine (SM) has been shown to have anti‐cancer properties. However, the underlying mechanism involved remains undetermined. We showed that SM inhibited the growth of non‐small cell lung cancer (NSCLC) cells, which was enhanced in cells with silencing of long non‐coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR), while it overcame by overexpression of HOTAIR. In addition, SM increased the expression of miR‐214‐3p and inhibited 3‐phosphoinositide‐dependent protein kinase‐1 (PDPK1) gene expression, which was strengthened by miR‐214‐3p mimics. Intriguingly, HOTAIR could directly bind to miR‐214‐3p and sequestered miR‐214‐3p from the target gene PDPK1. Intriguingly, overexpression of PDPK1 overcame the effects of SM on miR‐214‐3p expressions and neutralized the SM‐inhibited cell growth. Similar results were observed in vivo. In summary, our results showed that SM‐inhibited NSCLC cell growth through the reciprocal interaction between HOTAIR and miR‐214‐3p, which ultimately suppressed PDPK1 gene expression. HOTAIR effectively acted as a competing endogenous RNA (ceRNA) to stimulate the expression of target gene PDPK1. These complex interactions and feedback mechanisms contribute to the overall effect of SM. This unveils a novel molecular mechanism underlying the anti‐cancer effect of SM in human lung cancer.

show abstract

HOTAIR-mediated reciprocal regulation of EZH2 and DNMT1 contribute to polyphyllin I-inhibited growth of castration-resistant prostate cancer cells in vitro and in vivo

Cited by 48 publications

References 59 publications

Long Non-coding RNA LINC00114 Facilitates Colorectal Cancer Development Through EZH2/DNMT1-Induced miR-133b Suppression

Long Non-coding RNA LINC00114 Facilitates Colorectal Cancer Development Through EZH2/DNMT1-Induced miR-133b Suppression

HOTAIR: An Oncogenic Long Non-Coding RNA in Human Cancer

Novel reciprocal interaction of lncRNA HOTAIR and miR‐214‐3p contribute to the solamargine‐inhibited PDPK1 gene expression in human lung cancer

Contact Info

Product

Resources

About