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PLEKHO1 knockdown inhibits RCC cell viability in vitro and in vivo, potentially by the Hippo and MAPK/JNK pathways.

ABSTRACT: Renal cell carcinoma (RCC) is the most common type of kidney cancer. By analysing The Cancer Genome Atlas (TCGA) database, 16 genes were identified to be consistently highly expressed in RCC tissues compared with the matched para?tumour tissues. Using a high?throughput cell viability screening method, it was found that downregulation of only two genes significantly inhibited the viability of 786?O cells. Among the two genes, pleckstrin homology domain containing O1 (PLEKHO1) has never been studied in RCC, to the best of our knowledge, and its expression level was shown to be associated with the prognosis of patients with RCC in TCGA dataset. The upregulation of PLEKHO1 in RCC was first confirmed in 30 paired tumour and para?tumour tissues. Then, the effect of PLEKHO1 on cell proliferation and apoptosis was assessed in vitro. Additionally, xenograft tumour models were established to investigate the function of PLEKHO1 in vivo. The results showed that PLEKHO1 knockdown significantly inhibited cell viability and facilitated apoptosis in vitro and impaired tumour formation in vivo. Thus, PLEKHO1 is likely to be associated with the viability of RCC cells in vitro and in vivo. Further gene expression microarray and co?expression analyses showed that PLEKHO1 may be involved in the serine/threonine?protein kinase hippo and JNK signalling pathways. Together, the results of the present study suggest that PLEKHO1 may contribute to the development of RCC, and therefore, further study is needed to explore its potential as a therapeutic target.

SUBMITTER: Yu Z

PROVIDER: S-EPMC6561616 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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PLEKHO1 knockdown inhibits RCC cell viability in vitro and in vivo, potentially by the Hippo and MAPK/JNK pathways.

Yu Zi Z Li Qiang Q Zhang Gejun G Lv Chengcheng C Dong Qingzhuo Q Fu Cheng C Kong Chuize C Zeng Yu Y

International journal of oncology 20190530 1

Renal cell carcinoma (RCC) is the most common type of kidney cancer. By analysing The Cancer Genome Atlas (TCGA) database, 16 genes were identified to be consistently highly expressed in RCC tissues compared with the matched para‑tumour tissues. Using a high‑throughput cell viability screening method, it was found that downregulation of only two genes significantly inhibited the viability of 786‑O cells. Among the two genes, pleckstrin homology domain containing O1 (PLEKHO1) has never been studi ...[more]

PMID: 31180521

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Project description:Osteoarthritis (OA) is a common degenerative disease that is associated with the degradation of articular cartilage. Accumulating evidence has confirmed that LIM mineralization protein-1 (LMP-1) is an important agent of bone formation and has been shown to be osteoinductive in various types of disease. However, the underlying mechanisms of LMP-1 in the pathogenesis of OA remain unknown. The present study aimed to evaluate the role and potential mechanism of LMP-1 in IL-1β-stimulated OA chondrocytes. CHON-001 cells were transfected with pcDNA3.1-LMP-1, pcDNA3.1, negative control-small interfering (si)RNA or LMP-1 siRNA for 24 h and then induced by IL-1β for 12 h to establish an OA model in vitro. Cell viability, apoptosis and inflammatory cytokine (IL-6, IL-8 and TNF-α) release were assessed using MTT assay, ﬂow cytometry and ELISA, respectively. The expression levels of LMP-1, cleaved-caspase 3, phosphorylated (p)-p65, p65, p-JNK and JNK were analyzed using reverse transcription-quantitative PCR and western blotting. Overexpression of LMP-1 notably alleviated the IL-1β-induced inflammatory response in CHON-001 cells, as shown by increased cell viability, decreased apoptosis, suppressed expression of cleaved-caspase 3 and a decreased cleaved-caspase 3/caspase 3 ratio. Moreover, IL-1β-induced secretion of IL-6, IL-8 and TNF-α in CHON-001 cells; this was reversed by pcDNA3.1-LMP-1. However, knocking down LMP-1 expression exert opposite effects on the IL-1β-induced inflammatory response in CHON-001 cells, as evidenced by the decreased cell viability, increased apoptosis, enhanced expression of cleaved-caspase 3 and cleaved-caspase 3/caspase 3 ratio and enhanced secretion of IL-6, IL-8 and TNF-α observed. The present data demonstrated that LMP-1 siRNA notably inhibited LMP-1 expression, suppressed cell viability, promoted apoptosis and enhanced cleaved-caspase 3 expression and cleaved-caspase 3/caspase 3 ratio. In addition, LMP-1 siRNA promoted the release of inflammatory factors in CHON-001 cells. It was also found that pcDNA3.1-LMP-1 inhibited p-p65 and p-JNK expression, as well as decreasing the p-p65/p65 and p-JNK/JNK ratio. Nevertheless, there was no significant difference in the mRNA expression levels of p65 and JNK between the groups. Taken together, these findings indicated that overexpression of LMP-1 alleviated IL-1β-induced chondrocytes injury by regulating the NF-κB and MAPK/JNK pathways, suggesting that LMP-1 may be a valuable therapeutic agent for OA treatment.

Dataset Information

PLEKHO1 knockdown inhibits RCC cell viability in vitro and in vivo, potentially by the Hippo and MAPK/JNK pathways.

Publications

PLEKHO1 knockdown inhibits RCC cell viability in vitro and in vivo, potentially by the Hippo and MAPK/JNK pathways.

Similar Datasets

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