Effect of EH domain containing protein 2 on the biological behavior of clear cell renal cell carcinoma

Liu, C; Liu, S; Wang, L; Wang, Y; Li, Y; Cui, Yaya

doi:10.1177/0960327119842241

Cited by 10 publications

(12 citation statements)

References 26 publications

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“…It was confirmed that circEHD2 knock-down reduced SU-resistant cancer cells’ progression. Our study is in agreement with a previous investigation which confirmed that EHD2 elevation enhances RCC proliferation, migration and invasion [ 26 ]. Several studies have confirmed that circRNA has multiple sites to bind and control miRNA activity and modulate downstream target genes.…”

Section: Discussionsupporting

confidence: 94%

Circular RNA Eps15-homology domain-containing protein 2 induce resistance of renal cell carcinoma to sunitinib via microRNA-4731-5p/ABCF2 axis

Cao

2022

Bioengineered

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Circular RNAs (circRNAs) are linked with the occurrence and progression of renal cell carcinoma (RCC). However, circRNAs’ mechanism in developing resistance to RCC has not been clarified. This research assessed the role and mechanism of circular RNA circ Eps15-homology domain-containing protein 2 (EHD2) in the resistance of sunitinib (SU) to RCC. ACHN, 786-O, 769P, and HEK-293 T cells and RCC tissue samples were used for the investigations. The circEHD2 expression in RCC cells and tissues was determined through RT-qPCR. Association of circEHD2 with RCC histological grade of RCC was done through Chi-square. MiR-4731-5p, ABCF2, and circEHD2 were transfected into RCC cell lines. A dual-luciferase reporter assay was used to determine the interaction between miR-4731-5p, circEHD2, and ABCF2. MTT assay was used to analyze cell viability, while apoptosis was studied using flow cytometry. Colony-formation and transwell experiments were used to assess migration and invasion. The ATP Binding Cassette Subfamily F Member 2 (ABCF2) expression was analyzed through western blot. The results showed increased circEHD2 in SU-resistant RCC tissues and cell lines and implicated in RCC histological grade and SU resistance. Knock-down of circEHD2 down-regulated the resistance of RCC to SU in vitro and vivo ; circEHD2 bound to miR-4731-5p to mediate ABCF2 in RCC; ABCF2 rescued the inhibitory effect of circEHD2 knock-down on SU resistance of RCC. In conclusion, circEHD2 enhances RCC resistance to SU via acting as a miR-4731-5p sponge to mediate ABCF2. MiR-4731-5p can target circEHD2 and ABCF2, thus providing a novel and effective therapeutic against renal cell carcinoma.

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Section: Discussionsupporting

confidence: 94%

Circular RNA Eps15-homology domain-containing protein 2 induce resistance of renal cell carcinoma to sunitinib via microRNA-4731-5p/ABCF2 axis

Cao

2022

Bioengineered

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“…EHD2 knockdown promotes cell migration in oesophageal squamous cell carcinoma ( 48 ). Extensive studies have shown that lncRNAs containing miRNA binding sites can function as ceRNAs to regulate mRNAs in cancers, including OS ( 49 - 51 ). The ceRNA pattern mediated by TUSC8 also functions in other types of cancer.…”

Section: Discussionmentioning

confidence: 99%

TUSC8 inhibits the development of osteosarcoma by sponging miR‑197‑3p and targeting EHD2

et al. 2020

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Osteosarcoma (OS) is one of the most common malignant bone tumours and generally occurs in children and adolescents. Increasing evidence has demonstrated that dysregulated long non-coding RNAs (lncRNAs) play crucial roles in the progression of various human neoplasms. Among these, tumour suppressor candidate 8 (TUSc8) is a novel lncRNA and has been reported to function as a tumour suppressor in cervical cancer. However, the exact role of TUSc8 in OS remains largely unknown. In the present study, it was observed that TUSc8 was markedly downregulated in OS tissues and cell lines. Functional experiments demonstrated that the overexpression of TUSC8 significantly suppressed the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), whereas it accelerated the apoptosis of OS cells. Mechanistically, TUSc8 served as a sponge for miR-197-3p, and EH-domain containing 2 (EHd2) was identified as a downstream target molecule of miR-197-3p. Further investigations indicated that EHD2 knockdown significantly reversed the effects on OS cellular processes induced by TUSC8 overexpression. On the whole, these findings indicate that TUSc8 functions as a competing endogenous RNA (ceRNA) to suppress OS cell growth and EMT via the miR-197-3p/EHd2 axis. TUSc8 may thus function as a potential therapeutic target in OS treatment.

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“…By contrast, Liu et al demonstrated that EHD2 overexpression enhanced the proliferation, invasion, and migration but inhibited the apoptosis of clear cell renal cell carcinoma (ccRCC) cells, while EHD2 interference showed opposite functions. Interference of EHD2 can inhibit the development of ccRCC by inhibiting the cellular proliferation, invasion, and migration ( 26 ). In addition, EHD2 overexpression inhibits colon cancer cell proliferation, but enhances cell apoptosis and cell cycle arrest ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

EHD2 inhibits the invasive ability of lung adenocarcinoma and improves the prognosis of patients

Wei¹,

Shao²,

Wang³

et al. 2022

J Thorac Dis

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Background: EHD2 may be involved in tumorigenesis and development. However, the role of EHD2 in lung adenocarcinoma (LUAD) is unknown. Methods:The link between EHD2 and LUAD and the associated underlying mechanism was determined using bioinformatics analysis. Then, immunohistochemistry (IHC) was employed to detect EHD2 expression level in LUAD patients. The stable transfection cell line was used to establish with lentivirus vector, and then the transfection efficiency was detected by western blot. Phagokinetic motility assays, transwell assays, and western blotting were also employed to investigate EHD2 impacts on cell viability. Results:The results indicated that EHD2 protein expression in human LUAD samples was significantly lower than that in the adjacent normal tissues. Low EHD2 expression was significantly linked to lymph node metastasis as well as advanced tumor-node-metastasis (TNM) staging (P<0.05). The Kaplan-Meier survival curve showed that low EHD2 expression was significantly associated with low survival (P=0.01). The multivariate Cox regression analysis confirmed that EHD2 expression and TNM stage were independent prognostic factors for LUAD patients (all P<0.05). The in vitro experiments demonstrated that EHD2 knockdown markedly contributed to an increase in migration and invasion in A549 cells. Overexpression of EHD2 substantially suppressed H1299 cell migration and invasion. Furthermore, decreased E-cadherin expression was observed in A549 cells with EHD2 knockdown, as well as increased N-cadherin and vimentin expressions. By contrast, E-cadherin expression was increased in H1299 cells, whereas N-cadherin and vimentin expressions were decreased as a result of EHD2 overexpression.Conclusions: Our study demonstrated that EHD2 reduces LUAD migration and invasion by preventing the epithelial-mesenchymal transition (EMT) process. Furthermore, the results suggest that EHD2 may be a novel biomarker for prognosis prediction.

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Effect of EH domain containing protein 2 on the biological behavior of clear cell renal cell carcinoma

Cited by 10 publications

References 26 publications

Circular RNA Eps15-homology domain-containing protein 2 induce resistance of renal cell carcinoma to sunitinib via microRNA-4731-5p/ABCF2 axis

Circular RNA Eps15-homology domain-containing protein 2 induce resistance of renal cell carcinoma to sunitinib via microRNA-4731-5p/ABCF2 axis

TUSC8 inhibits the development of osteosarcoma by sponging miR‑197‑3p and targeting EHD2

EHD2 inhibits the invasive ability of lung adenocarcinoma and improves the prognosis of patients

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