Evidence map›Paper›PMID 36849889›Full record

ArticleClinical epigenetics2023

Phospholipase C delta 1 inhibits WNT/β-catenin and EGFR-FAK-ERK signaling and is disrupted by promoter CpG methylation in renal cell carcinoma.

Jianlian Xie, Jun Zhou, Jiliang Xia, Ying Zeng, Guo Huang, Weihong Zeng, Tingyu Fan, Lili Li, Xi Zeng, Qian Tao

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 9 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Jianlian Xie *Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Jun Zhou *Hunan Province Key Laboratory of Tumor Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Jiliang XiaHunan Province Key Laboratory of Tumor Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Ying ZengHunan Province Key Laboratory of Tumor Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Guo HuangHunan Province Key Laboratory of Tumor Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Weihong ZengHunan Province Key Laboratory of Tumor Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Tingyu FanHunan Province Key Laboratory of Tumor Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Lili LiCancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Xi ZengHunan Province Key Laboratory of Tumor Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. xzeng@usc.edu.cn.
Qian TaoCancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China. qtao@cuhk.edu.hk.
University of South China · CNChinese University of Hong Kong · HK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPLCD1, located at 3p22, encodes an enzyme that mediates cellular metabolism and homeostasis, intracellular signal transduction and movement. PLCD1 plays a pivotal role in tumor suppression of several types of cancers; however, its expression and underlying molecular mechanisms in renal cell carcinoma (RCC) pathogenesis remain elusive.

methodsRT-PCR and Western blot were used to detect PLCD1 expression in RCC cell lines and normal tissues. Bisulfite treatment, MSP and BGS were utilized to explore the CpG methylation status of PLCD1 promoter. Online databases were analyzed for the association between PLCD1 expression/methylation and patient survival. In vitro experiments including CCK8, colony formation, wound-healing, transwell migration and invasion, immunofluorescence and flow cytometry assays were performed to evaluate tumor cell behavior. Luciferase assay and Western blot were used to examine effect of PLCD1 on WNT/β-catenin and EGFR-FAK-ERK signaling.

resultsWe found that PLCD1 was widely expressed in multiple adult normal tissues including kidney, but frequently downregulated or silenced in RCC due to its promoter CpG methylation. Restoration of PLCD1 expression inhibited the viability, migration and induced G2/M cell cycle arrest and apoptosis in RCC cells. PLCD1 restoration led to the inhibition of signaling activation of WNT/β-catenin and EGFR-FAK-ERK pathways, and the EMT program of RCC cells.

conclusionsOur results demonstrate that PLCD1 is a potent tumor suppressor frequently inactivated by promoter methylation in RCC and exerts its tumor suppressive functions via suppressing WNT/β-catenin and EGFR-FAK-ERK signaling. These findings establish PLCD1 as a promising prognostic biomarker and treatment target for RCC.

Indexed as

Carcinoma, Renal CellKidney NeoplasmsAdultbeta CateninDNA MethylationErbB ReceptorsHumansPhospholipase C deltaSignal Transductionbeta CateninEGFR protein, humanErbB ReceptorsPhospholipase C deltaPLCD1 protein, humanCpG methylationEMTPLCD1RCCWNT/β-catenin

Identifiers

PMID36849889
PMCPMC9972803
OpenAlexW4322494691

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.