Long noncoding RNA SNHG12 promotes tumour progression and sunitinib resistance by upregulating CDCA3 in renal cell carcinoma

Chen

BioMed Research International

et al. 2021

Cell division cycle-associated protein-3 (CDCA3) contributes to the regulation of the cell cycle. CDCA3 plays an important role in the carcinogenesis of various cancers; however, the association between CDCA3 expression, prognosis of patients, and immune infiltration in the tumor microenvironment is still unknown. Here, we demonstrated that CDCA3 was differentially expressed between the tumor tissues and corresponding normal tissues using in silico analysis in the ONCOMINE and Tumor Immune Estimation Resource (TIMER) databases. We analyzed the relationship between the expression of CDCA3 and prognosis of patients with hepatocellular carcinoma (HCC) using the Kaplan–Meier plotter database and Gene Expression Profiling Interactive Analysis (GEPIA). Furthermore, we determined the prognostic value of CDCA3 expression using univariate and multivariate analyses. We observed that CDCA3 expression closely correlated with immune infiltration and gene markers of infiltrating immune cells in the TIMER database. CDCA3 was highly expressed in the tumor tissues than in the adjacent normal tissues in various cancers, including HCC. Increased expression of CDCA3 was accompanied by poorer overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). The correlation between CDCA3 expression and OS and disease-free survival (DFS) was also studied using GEPIA. CDCA3 expression was associated with the levels of immune cell infiltration and was positively correlated with tumor purity. Moreover, CDCA3 expression was associated with gene markers such as PD-1, CTLA4, LAG3, and TIM-3 from exhausted T cells, CD3D, CD3E, and CD2 from T cells, and TGFB1 and CCR8 located on the surface of Tregs. Thus, we demonstrated that CDCA3 may be a potential target and biomarker for the management and diagnosis of HCC.

Section: Discussionmentioning

confidence: 99%

CDCA3 Is a Novel Prognostic Biomarker Associated with Immune Infiltration in Hepatocellular Carcinoma

Chen

BioMed Research International

et al. 2021

“…Moreover, besides exerting a cycle-regulating effect, CDCA3 could contribute to chemoresistance in breast cancer [ 27 ] and renal cell carcinoma [ 28 ]. In addition, the elevated status of CDCA3 mRNA is regulated by DNA hypomethylation mediated by SP1 [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

The inhibitory effect of silencing CDCA3 on migration and proliferation in bladder urothelial carcinoma

et al. 2021

Background CDCA3 is an important component of the E3 ligase complex with SKP1 and CUL1, which could regulate the progress of cell mitosis. CDCA3 has been widely identified as a proto-oncogene in multiple human cancers, however, its role in promoting human bladder urothelial carcinoma has not been fully elucidated. Methods Bioinformatic methods were used to analyze the expression level of CDCA3 in human bladder urothelial carcinoma tissues and the relationship between its expression level and key clinical characteristics. In vitro studies were performed to validate the specific functions of CDCA3 in regulating cell proliferation, cell migration and cell cycle process. Alterations of related proteins was investigated by western blot assays. In vivo studies were constructed to validate whether silencing CDCA3 could inhibit the proliferation rate in mice model. Results Bioinformatic analysis revealed that CDCA3 was significantly up-regulated in bladder urothelial carcinoma samples and was related to key clinical characteristics, such as tumor grade and metastasis. Moreover, patients who had higher expression level of CDCA3 tend to show a shorter life span. In vitro studies revealed that silencing CDCA3 could impair the migration ability of tumor cells via down-regulating EMT-related proteins such as MMP9 and Vimentin and inhibit tumor cell growth via arresting cells in the G1 cell cycle phase through regulating cell cycle related proteins like p21. In vivo study confirmed that silencing CDCA3 could inhibit the proliferation of bladder urothelial carcinoma cells. Conclusions CDCA3 is an important oncogene that could strengthen the migration ability of bladder urothelial carcinoma cells and accelerate tumor cell growth via regulating cell cycle progress and is a potential biomarker of bladder urothelial carcinoma.

“…[121][122][123] Several studies demonstrated that the lncRNA SNHGs function as the important regulators in the development of tumorigenesis. 124,125 SNHG1 acts as a ceRNA to antagonize the effect of miR-137 and elicit RCC progression and metastasis. The overexpression of SNHG1 also predicts the poor prognosis of RCC.…”

Section: Pancreatic Cancermentioning

confidence: 99%

Small nucleolar RNA host genes promoting epithelial–mesenchymal transition lead cancer progression and metastasis

Biagioni¹,

Tavakol

Ahmadirad

et al. 2021

IUBMB Life

The small nucleolar RNA host genes (SNHGs) belong to the long non-coding RNAs and are reported to be able to influence all three levels of cellular information-bearing molecules, that is, DNA, RNA, and proteins, resulting in the generation of complex phenomena. As the host genes of the small nucleolar RNAs (snoRNAs), they are commonly localized in the nucleolus, where they exert multiple regulatory functions orchestrating cellular homeostasis and differentiation as well as metastasis and chemoresistance. Indeed, worldwide literature has reported their involvement in the epithelial-mesenchymal transition (EMT) of different histotypes of cancer, being able to exploit peculiar features, for example, the possibility to act both in the nucleus and the cytoplasm. Moreover, SNHGs regulation is a fundamental topic to better understand their role in tumor progression albeit such mechanism is still debated. Here, we reviewed the biological functions of SNHGs in particular in the EMT process and discussed the perspectives for new cancer therapies.