<i>ARID1A</i> knockdown triggers epithelial‐mesenchymal transition and carcinogenesis features of renal cells: role in renal cell carcinoma

Somsuan, Keerakarn; Peerapen, Paleerath; Boonmark, Wanida; Plumworasawat, Sirikanya; Samol, Ratirath; Sakulsak, Natthiya; Thongboonkerd, Visith

doi:10.1096/fj.201802720rr

Cited by 36 publications

(29 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Epithelial-mesenchymal transition (EMT) plays an important role in cancer development and progression (18). Somsuan et al found in 2019 that ARId1A knockout promoted EMT in cells, which was characterized by an increased fusiform index and stromal markers, decreased epithelial markers, and enhanced renal cell migration activity and drug resistance (19). Wilson et al in 2019 also indicated that the abnormal endometrial tissue diffusion was closely related to the increase in EMT-related gene expression induced by ARId1A deletion (20).…”

Section: Role Of Arid1a In Epithelial-mesenchymal Transition In Breasmentioning

confidence: 99%

Role of ARID1A in epithelial‑mesenchymal transition in�breast cancer and its effect on cell sensitivity to 5‑FU

et al. 2020

View full text Add to dashboard Cite

The loss of function mutation of AT-rich interactive domain 1A (ARId1A) often occurs in patients with breast cancer. It has been found that ARId1A knockout can enhance both the migratory activity of renal carcinoma cells and their sensitivity to therapeutic drugs by promoting epithelialmesenchymal transition (EMT); however, its mechanisms of action in breast cancer remain unclear. In the present study, immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPcR) revealed that the expression of ARID1A in breast cancer tissues was significantly lower than that in paracancerous tissues, and patients with a low ARId1A expression had a lower survival rate. ARId1A was expressed at low levels in breast cancer cells. In addition, siRNA targeting ARId1A (siARId1A) and ARId1A overexpression vector were transfected into McF7 and MdA-MB-231 cells, respectively. Proliferation assay revealed that ARId1A silencing increased cell viability and partially reversed the inhibitory effects of 5-fluorouracil (5-FU) on the McF7 cells, while ARId1A overexpression exerted an opposite effect on the MdA-MB-231 cells. ARId1A silencing promoted proliferation, migration, invasion and angiogenesis, and partly reversed the inhibitory effects of 5-FU on cell biological behaviors, while the overexpression of ARId1A further enhanced the inhibitory effect of 5-FU on the cells. Furthermore, ARId1A regulated the migration and invasion of breast cancer cells through EMT. On the whole, the findings of the present study demonstrate that ARId1A exerts an antitumor effect on breast cancer, and its overexpression can enhance the sensitivity of breast cancer cells to 5-FU.

show abstract

Section: Role Of Arid1a In Epithelial-mesenchymal Transition In Breasmentioning

confidence: 99%

Role of ARID1A in epithelial‑mesenchymal transition in�breast cancer and its effect on cell sensitivity to 5‑FU

et al. 2020

View full text Add to dashboard Cite

show abstract

“…A wide range of cancer-gene mutations are detected by NGS and loss of function mutations in the ARID1A is detected repeatedly and frequently in various cancer types [13,21]. A recent study revealed that ARID1A knockdown in renal cells led to epithelial-mesenchymaltransition, highlighting its role in cell differentiation and tissue homeostasis [22].…”

Section: Introductionmentioning

confidence: 99%

Altered ARID1A expression in colorectal cancer

et al. 2020

View full text Add to dashboard Cite

Background: ARID1A has been described as a tumor suppressor gene, participating in chromatin re-modeling, epithelial-mesenchymal-transition and many other cellular and molecular processes. It has been cited as a contribute in tumorigenesis. The role of ARID1A in CRC is not yet defined. Aim: To investigate the role of ARID1A methylation and CNV in its expression in CRC cell lines and to examine the relationship between ARID1A status with survival and clinicopathologic characteristics in patients with CRC. Methods: We used RT-PCR to determine both CNV and expression of ARID1A from six CRC cell lines. We used MSP to evaluate methylation of ARID1A. IHC was used to assess ARID1A protein expression. We also evaluated MSI and EMAST status in 18 paired CRC and adjacent normal tissues. 5AzadC was used to assess effect of DNA demethylation on ARID1A expression. Statistical analysis was performed to establish correlations between ARID1A expression and other parameters. Results: Among the 18 CRC tumors studied, 7 (38.8%) and 5 tumors (27.7%) showed no or low ARID1A expression, respectively. We observed no significant difference in ARID1A expression for overall patient survival, and no difference between clinicopathological parameters including MSI and EMAST. However, lymphatic invasion was more pronounced in the low/no ARID1A expression group when compared to moderate and high expression group (33% VS. 16.6% respectively. ARID1A promoter methylation was observed in 4/6 (66%) cell lines and correlated with ARID1A mRNA expression level ranging from very low in SW48, to more pronounced in HCT116 and HT-29/219. Treatment with the methyltransferase inhibitor 5-Azacytidine (5-aza) resulted in a 25.4-fold and 6.1-fold increase in ARID1A mRNA expression in SW48 and SW742 cells, respectively, while there was no change in SW480 and LS180 cells. No ARID1A CNV was observed in the CRC cell lines. Conclusion: ARID1A expression is downregulated in CRC tissues which correlates with it being a tumor suppressor protein. This finding confirms ARID1A loss of expression in CRC development. Our in-vitro results suggest high methylation status associates with reduced ARID1A expression and contributes to CRC tumorigenesis. However, there was no significant association between ARID1A loss of expression and clinicopathological characteristics. Future in-vivo analysis is warranted to further establish ARID1A role in colorectal neoplastic transformation.

show abstract

“…The results showed that HDACi not only suppress the EMT but also compromise DNA repair processes of cancer cells [37]. The involvement of EMT was confirmed in another recent paper [38], where they observed that the knockdown of AT-rich interactive domain 1A (ARID1A), a novel tumour suppressor gene, by siRNA both in non-malignant MDCK and malignant 786-O RCC cells, triggers EMT. The down-regulation of ARID1A protein expression was confirmed also in human RCC tissues.…”

Section: Cultured Cellsmentioning

confidence: 59%

Prognostic significance of proteomics and multi-omics studies in renal carcinoma

Raimondo

Pitto

2020

Expert Review of Proteomics

View full text Add to dashboard Cite

Introduction Renal carcinoma and in particular its most common variant, the clear cell subtype, is often diagnosed incidentally through abdominal imaging. Rather frequently, the tumour is discovered at an early stage. However, 20% to 40% of patients undergoing nephrectomy for clinically localized renal cancer, even after accurate histological and clinical classification, will develop metastasis or recurrence, justifying the associated mortality rate. Therefore, even if renal carcinoma is not among the most frequent nor deadly cancers, a better prognostication is needed.Areas covered Recently proteomics or other -omics combinations have been applied to both cancer tissues, on the neoplasia itself and surrounding microenvironment, cultured cells and biological fluids (so-called liquid biopsy) generating a list of prognostic molecular tools that will be reviewed in the present paper. Expert opinion.Although promising, none of the approaches listed above has been yet translated in clinics. This is likely due to the peculiar genetic and phenotypic heterogeneity of this cancer, which makes nearly each tumour different from all the others. Attempts to overcome this issue will be also revised. In particular we will discuss how the application of -omics integrated approaches could provide the determinants of response to the different targeted drugs.

show abstract

ARID1A knockdown triggers epithelial‐mesenchymal transition and carcinogenesis features of renal cells: role in renal cell carcinoma

Cited by 36 publications

References 65 publications

Role of ARID1A in epithelial‑mesenchymal transition in�breast cancer and its effect on cell sensitivity to 5‑FU

Role of ARID1A in epithelial‑mesenchymal transition in�breast cancer and its effect on cell sensitivity to 5‑FU

Altered ARID1A expression in colorectal cancer

Prognostic significance of proteomics and multi-omics studies in renal carcinoma

Contact Info

Product

Resources

About