Long noncoding RNA HOTAIR regulates the invasion and metastasis of prostate cancer by targeting hepaCAM

Li, Ting; Liu, Nanjing; Gao, Yingying; Quan, Zhen; Hao, Yanbin; Yu, Chao-wen; Li, Luo; Yuan, Mengjuan; Luo, Chunli; Wu, Xiaohou

doi:10.1038/s41416-020-01091-1

Cited by 29 publications

(14 citation statements)

References 35 publications

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“…Literature indicates that the expression of HepaCAM expression is always reduced, or completely lost in many cancers, including prostate cancer. 13,14 However, systematic studies of CRPC are rare.…”

Section: Discussionmentioning

confidence: 99%

“…13 Furthermore, HOTAIR is known to inhibit HepaCAM transcription, thus promoting prostate cancer metastasis via MAPK signaling. 14 Numerous studies indicate that the HepaCAM gene acts as a tumor suppressor candidate that may be downregulated during cancer development. However, the actual pathological mechanism responsible for how HepaCAM affects the metastasis of prostate cancer has not been fully elucidated, particularly in castrationresistant cancer cell types.…”

Section: Introductionmentioning

confidence: 99%

“…The upregulation of HepaCAM inhibits the vitality of prostate cancer cells by inhibiting ERK signaling and disrupting the nucleus translocation of the AR 13 . Furthermore, HOTAIR is known to inhibit HepaCAM transcription, thus promoting prostate cancer metastasis via MAPK signaling 14 . Numerous studies indicate that the HepaCAM gene acts as a tumor suppressor candidate that may be downregulated during cancer development.…”

Section: Introductionmentioning

confidence: 99%

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STAT3 phosphorylation is required for the HepaCAM‐mediated inhibition of castration‐resistant prostate cancer cell viability and metastasis

et al. 2021

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Background Castration‐resistant prostate cancer (CRPC) is an advanced disease that is difficult to treat, the mechanism of it is unclear. This study illustrated the function of hepatocyte cell adhesion molecule (HepaCAM) on CRPC cell viability and metastasis. Methods The expression of HepaCAM and p‐STAT3 in CRPC tissues were determined by immunohistochemistry and western blot analysis. Cell Counting Kit‐8 and colony formation assays were deployed to analyze the growth ability of CRPC cells following the adenovirus‐mediated re‐expression of HepaCAM. CRPC cell migration and invasion capacity were investigated by wound healing and Matrigel‐coated transwell assays, respectively. The messenger RNA or protein levels of p‐STAT3, CyclinD1, cMyc, MMP2, MMP9, and VEGF were determined by reverse transcription (RT) followed by quantitative real‐time polymerase chain reaction (RT‐qPCR), and western blot analysis after either HepaCAM re‐expression alone or in combination with IL‐22 treatment. A CRPC orthotopic xenograft mouse model was applied to investigate the functional effect of HepaCAM on the metastasis of CRPC cells to the lungs. Results The expression levels of HepaCAM were decreased while those of p‐STAT3 were elevated in CRPC cells compare with surrounding benign tissues (p < .001). The overexpression of HepaCAM in CRPC cells notably reduced proliferation, migration, and invasion by inhibiting the expression of p‐STAT3, CyclinD1, cMyc, MMP2, MMP9, and VEGF (p < .05). In addition, the expression of HepaCAM significantly inhibited the IL‐22/p‐STAT3 axis and the metastasis of CRPC cells to the lungs. Conclusions Our data suggested that HepaCAM suppressed the viability of CRPC cells via the IL‐22/p‐STAT3 axis and inhibited the metastasis of CRPC cells from the prostate to the lungs (p < .05).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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STAT3 phosphorylation is required for the HepaCAM‐mediated inhibition of castration‐resistant prostate cancer cell viability and metastasis

et al. 2021

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“…As one of the epigenetic modulation manners, histone methylation modification exerts multiple effects on gene transcription (13)(14)(15). Methylation modification at some specific lysine activates gene transcription, and whereas methylation modification at other lysine represses gene transcription, such as the classical repressive histone marker tri-methylation of histone H3 at lysine 27 (H3K27me3) (16)(17)(18). In our previous study, we found an HCC-related histone lysine methyltransferase NSD1 (nuclear receptor binding SET domaincontaining protein 1), which catalyses di-methylation of histone H3 at lysine 36 (H3K36me2) (19).…”

Section: Introductionmentioning

confidence: 99%

KB-68A7.1 Inhibits Hepatocellular Carcinoma Development Through Binding to NSD1 and Suppressing Wnt/β-Catenin Signalling

Zhang

Cao

et al. 2022

Front. Oncol.

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Hepatocellular carcinoma (HCC) is one of the most lethal malignancies with extremely poor prognosis. Therefore, revealing the critical molecules involved in HCC progression and prognosis is urgently needed. In this study, through combining public dataset and our cohort, we found a novel prognosis-related long non-coding RNA KB-68A7.1 in HCC. KB-68A7.1 was lowly expressed in HCC, whose low expression was associated with large tumour size, aggressive clinical characteristic, and poor survival. Gain- and loss-of-function assays demonstrated that KB-68A7.1 restricted HCC cellular proliferation, induced HCC cellular apoptosis, and suppressed HCC cellular migration and invasion in vitro. Xenograft assays demonstrated that KB-68A7.1 suppressed HCC tumour growth and metastasis in vivo. These functional assays suggested KB-68A7.1 as a tumour suppressor in HCC. Histone methyltransferase nuclear receptor binding SET domain-containing protein 1 (NSD1) was found to bind to KB-68A7.1. KB-68A7.1 was mainly distributed in the cytoplasm. The binding of KB-68A7.1 to NSD1 sequestrated NSD1 in the cytoplasm, leading to the reduction in nuclear NSD1 level. Through decreasing nuclear NSD1 level, KB-68A7.1 reduced di-methylation of histone H3 at lysine 36 (H3K36me2) and increased tri-methylation of histone H3 at lysine 27 (H3K27me3) at the promoter of WNT10B, a target of NSD1. Thus, KB-68A7.1 repressed WNT10B transcription. The expression of WNT10B was negatively correlated with that of KB-68A7.1 in HCC tissues. Through repressing WNT10B, KB-68A7.1 further repressed Wnt/β-catenin signalling. Functional rescue assays showed that overexpression of WNT10B reversed the tumour-suppressive roles of KB-68A7.1, whereas the oncogenic roles of KB-68A7.1 depletion were abolished by Wnt/β-catenin signalling inhibitor. Overall, this study identified KB-68A7.1 as a lowly expressed and prognosis-related lncRNA in HCC, which suppressed HCC progression through binding to NSD1 and repressing Wnt/β-catenin signalling.

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“…For instance, lncRNA LEF1-AS1 upgrades androgen-independent PCa progression via the upregulation of FZD2 and CD44 14 and lncRNA HOTAIR advances the invasion and metastasis of PCa by activating MAPK pathway. 15 …”

Section: Introductionmentioning

confidence: 99%

Long Noncoding RNA AATBC Promotes the Proliferation and Migration of Prostate Cancer Cell Through miR-1245b-5p/CASK Axis

Zhang¹,

Liu²,

Zhao³

et al. 2021

CMAR

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Introduction Long noncoding RNAs (lncRANs) as suppressive or oncogenic genes have been substantiated in prostate cancer (PCa). In the current study, the role and molecular mechanism of lncRNA AATBC in the progression of PCa was evaluated. Methods LncRNA AATBC and miR-1245b-5p expression were evaluated using RT-qPCR. CCK-8, colony-formation, apoptosis and transwell assay were used to analyze the in vitro role. The xenograft model was used to explore the in vivo role. Bioinformatics analysis and a dual luciferase assay, RIP and RNA pull down were used to confirm the interaction between lncRNA AATBC and 1245b-5p, as well as 1245b-5p and CASK. Results Firstly, we certified that the expression of AATBC was augmented in PCa, and knockdown of AATBC could significantly inhibit the growth of PCa in vitro and in vivo. Mechanistically, our results manifested that AATBC could directly bind to miR-1245b-5p. In addition, miR-1245b-5p played cancer-suppressive role in PCa cells. Moreover, CASK was attested as the target of miR-1245b-5p, and CASK was demonstrated to exert as oncogene in the progression of PCa. Finally, rescue assays illustrated that miR-1245b-5p downregulation or CASK restoration could greatly resist the restrained effects of AATBC knockdown on PCa progression. Conclusion AATBC could accelerate the progression of PCa through regulating miR-1245b-5p/CASK axis, which provided a potential therapeutic target for PCa treatment.

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Long noncoding RNA HOTAIR regulates the invasion and metastasis of prostate cancer by targeting hepaCAM

Cited by 29 publications

References 35 publications

STAT3 phosphorylation is required for the HepaCAM‐mediated inhibition of castration‐resistant prostate cancer cell viability and metastasis

STAT3 phosphorylation is required for the HepaCAM‐mediated inhibition of castration‐resistant prostate cancer cell viability and metastasis

KB-68A7.1 Inhibits Hepatocellular Carcinoma Development Through Binding to NSD1 and Suppressing Wnt/β-Catenin Signalling

Long Noncoding RNA AATBC Promotes the Proliferation and Migration of Prostate Cancer Cell Through miR-1245b-5p/CASK Axis

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