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.

Verteporfin treatment controls morphology, phenotype, and global gene expression for cells of the human nucleus pulposus

“…Examining the expression of genes within the ontology term Regulation of Cell Shape (GO: 0008360) provides insight into the mechanisms by which cell shape may be driving NP phenotype. While the expression profiles of the genes GNA13, BAMBI, PLEKHO1, SEMA4D, and EPB41 vary, the proteins for all five of these genes are implicated in intracellular pathways (eg, Wnt, TGF‐β, PI3K‐AKT, and Hippo) as well as cellular functions including control of cell shape, cell migration, response to hypoxia, regulation of cell viability, differentiation and production of ECM proteins 101‐110 . GNA13 (G Protein Subunit Alpha 13) is a member of the guanine nucleotide‐binding protein family and is known to be involved in numerous transmembrane signaling pathways including RhoA/ROCK signaling (Uniprot) as well as Wnt and Hippo pathways, 111,112 upstream of cellular processes including cell shape, actomyosin‐contractility, migration, and cytoskeletal remodeling 112,113 .…”

“…While the expression profiles of the genes GNA13, BAMBI, PLEKHO1, SEMA4D, and EPB41 vary, the proteins for all five of these genes are implicated in intracellular pathways (eg, Wnt, TGF-β, PI3K-AKT, and Hippo) as well as cellular functions including control of cell shape, cell migration, response to hypoxia, regulation of cell viability, differentiation and production of ECM proteins. [101][102][103][104][105][106][107][108][109][110] functioning of membrane proteins and cell adhesion molecules. [114][115][116] Differences observed in expression of these genes are illustrative of the complex regulation used by cells to sense and respond to their mechanical and biochemical environment.…”

Identification and Verification of Tumor Immune Microenvironment-Related Prognostic Genes in Kidney Renal Clear Cell Carcinoma

“…PLEKHO1 affects tumor cell proliferation and apoptosis. Downregulation of PLEKHO1 impairs RCC progression [ 27 ]. In our study, PLEKHO1 was found to be highly expressed in monocyte and DC.…”

A Four-MicroRNA Panel in Serum as a Potential Biomarker for Screening Renal Cell Carcinoma

“…Also, tribbles pseudokinase 3 (TRIB3) regulated tumor progression by activating the MAPK signaling pathway to accelerate the proliferation, migration, and invasion of RCC (Hong et al, 2019). Also, pleckstrin homology domain-containing O1 (PLEKHO1) might promote the development of RCC by the Hippo and MAPK/JNK pathways in vitro and in vivo (Yu et al, 2019). Also, miR-106 b could promote RCC progression by targeting Capicua through MAPK signaling (Miao et al, 2019).…”