ArticleCell death & disease2020
ZHX2 drives cell growth and migration via activating MEK/ERK signal and induces Sunitinib resistance by regulating the autophagy in clear cell Renal Cell Carcinoma.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
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.
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.
Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Beyond hypoxia and ccRCC: the expanding universe of VHL novel targets and next-generation therapeutics.Biomarker research · 2026Review
- ZHX2 Alleviates Vascular Remodeling and Smooth Muscle Cell Proliferation by Transcriptional Regulation of GADD45G.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Identification of methylation-sensitive human transcription factors using meSMiLE-seq.Nature communications · 2026Article
- Insights into the mechanisms of drug resistance in renal cell carcinoma: from multi-omics perspective.International journal of surgery (London, England) · 2026Article
- Liquid-liquid phase separation of ZHX2 protects DLBCL cells against ferroptosis through induction of SLC3A2.Leukemia · 2025Article
- Review
- Aquaporin 9 downregulation in KRASScientific reports · 2025Article
- MAGI3 enhances sensitivity to sunitinib in renal cell carcinoma by suppressing the MAS/ERK axis and serves as a prognostic marker.Cell death & disease · 2025Article
- Inhibition of primary cilia-hedgehog signaling axis triggers autophagic cell death and suppresses malignant progression of VHL wild-type ccRCC.Cell death & disease · 2024Article
- Genetics, Pathophysiology, and Current Challenges in Von Hippel-Lindau Disease Therapeutics.Diagnostics (Basel, Switzerland) · 2024Review
- An oncogenic role of lncRNA SNHG1 promotes ATG7 expression and autophagy involving tumor progression and sunitinib resistance of Renal Cell Carcinoma.Cell death discovery · 2024Article
- Article
- Article
- ZHX2 deficiency enriches hybrid MET cells through regulating E-cadherin expression.Cell death & disease · 2023Article
- Zinc fingers and homeoboxes 2 inhibition could suppress the proliferation of ovarian cancer cells by apoptosis pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Decreased zinc-fingers and homeoboxes family expression was associated with unfavorable outcomes and immune infiltration in lung adenocarcinoma.Translational cancer research · 2023Article
- Article
- Identification of Glucocorticoid Receptor Target Genes That Potentially Inhibit Collagen Synthesis in Human Dermal Fibroblasts.Biomolecules · 2023Article
- The m6A-regulation and single cell effect pattern in sunitinib resistance on clear cell renal cell carcinoma: Identification and validation of targets.Frontiers in pharmacology · 2023Article
- Histone methyltransferase SETD2: An epigenetic driver in clear cell renal cell carcinoma.Frontiers in oncology · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zinc fingers and homeoboxes 2 (ZHX2) was found as a novel VHL substrate target, and acted as an oncogenic driver in ccRCC. However, the detailed mechanism of ZHX2 in ccRCC development remains elusive, and no research has focused on studying ZHX2 in drug resistance yet. A tissue microarray with 358 ccRCC samples was used to determine the expression of ZHX2 in ccRCC patients. VHL-deficient cell line 786-O and VHL-normal cell line CAKI-1 was used for lineage reprogramming by transfecting with lentivirus. The in vitro and in vivo experiments were performed with these new cell lines to determine the mechanism of ZHX2 in ccRCC development and drug resistance. Immunohistochemistry analysis showed that ZHX2 was not highly expressed in ccRCC tumor tissues, only 33.2% (119/358) patients have high ZHX2 expression. However, high ZHX2 was significantly associated with advanced Fuhrman grade (p = 0.004), and proved to be an independent prognosis factor for progression-free survival (p = 0.0003), while there is no significant correlation with overall survival. We further discovered that ZHX2 overexpression could increase VEGF secretion and transcriptional activate the MEK/ERK1/2 and promote its downstream targets. We also found ZHX2 overexpression induce Sunitinib resistance though activating autophagy and the combination treatment of Sunitinib and Chloroquine could significantly rescue the phenomenon. In summary, these results indicate that ZHX2 drivers cell growth, migration though increase VEGF expression, and transcriptional activate MEK/ERK1/2 signaling pathway, and could induce Sunitinib resistance by regulating self-protective autophagy, these may provide new insight in advanced ccRCC treatment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.