Twist2 promotes kidney cancer cell proliferation and invasion by regulating ITGA6 and CD44 expression in the ECM-receptor interaction pathway

Zhang, Haojie; Ji, Tao; Lü, Sheng; Hu, Xin; Rong, Ruiming; Xu, Ming; Zhu, Tongyu

doi:10.2147/ott.s96535

Cited by 46 publications

(33 citation statements)

References 37 publications

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“…Currently, there are literature reports on using FAK as a novel potential biological target to investigate targeted therapy of NSCLC ( 39 , 40 ). The ECM-receptor interaction signalling pathway mediates the expression of enriched genes and regulates functions of these genes to promote tumour cell proliferation and migration and participate in tumour metastasis and infiltration ( 41 , 42 ). In NSCLC unrelated to smoking, the ECM-receptor interaction signalling pathway plays a critical role ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of HOXA3 in lung adenocarcinoma and its relevant molecular mechanism analysed by RT-qPCR, TCGA and in silico analysis

Gan

Wei

et al. 2018

Int J Oncol

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Recent studies have indicated that homeobox A3 (HOXA3) functions as a carcinogen in colon cancer and the methylation level of HOXA3 is significantly increased in lung adenocarcinoma (LUAD) tissues. However, at least to the best of our knowledge, few studies to date have been performed on HOXA3 in non-small cell lung cancer (NSCLC). Therefore, further studies on HOXA3 expression in NSCLC and the potential regulatory mechanisms are urgently required. In this study, HOXA3 expression in 55 tissues of cases of NSCLC and corresponding non-lung cancer tissues was detected by reverse transcription-quantitative PCR (RT-qPCR). In addition, the clinical significance of HOXA3 expression in NSCLC was evaluated using the Cancer Genome Atlas (TCGA) database. Bioinformatics analysis was then performed to elucidate the potential molecular mechanisms of action of HOXA3. Furthermore, the potential target microRNAs (miRNAs or miRs) of HOXA3 were predicted using miRWalk2.0. Based on Gene Expression Omnibus (GEO) and TGCA databases, standardized mean difference (SMD) and sROC methods were used for meta-analyses of the expression of potential target miRNAs of HOXA3 in NSCLC to evaluate their association with HOXA3. The results revealed that the HOXA3 expression levels in NSCLC, LUAD and lung squamous cell carcinoma (LUSC) were 0.1130±0.1398, 0.1295±0.16890 and 0.0906±0.0846, respectively. These values were all decreased compared with the normal tissues (0.1877±0.1975, 0.2337±0.2405 and 0.1249±0.0873, respectively, P<0.05). The TCGA database also revealed the low expression trend of HOXA3. The downregulation of HOXA3 may play an important role in the progression and the poor prognosis of LUAD. The TCGA database also suggested that HOXA3 in LUAD and LUSC tissues exhibited certain mutational levels. In addition, the methylation levels in the NSCLC, LUAD and LUSC tissues significantly increased [NSCLC: fold change (FC), 1.3226; P<0.001; LUAD: FC, 1.2712; P<0.001; and LUSC: FC, 1.3786; P<0.001]. According to the analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG), we found that the co-expression HOXA3 genes were mainly associated with the focal adhesion signalling pathway and the ECM-receptor interaction signalling pathway. Furthermore, the predicted miRNA, miR-372-3p, exhibited a high expression in both the NSCLC and LUAD tissues (P<0.05). On the whole, the findings of this study indicate that low HOXA3 expression may play a certain role in LUAD; however, its association with LUSC still requires further investigation. HOXA3 function may be achieved through different pathways or target miRNAs. However, the specific underlying mechanisms need to be confirmed through various functional studies.

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Section: Discussionmentioning

confidence: 99%

Downregulation of HOXA3 in lung adenocarcinoma and its relevant molecular mechanism analysed by RT-qPCR, TCGA and in silico analysis

Gan

Wei

et al. 2018

Int J Oncol

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“…In fact, after binding with HA, CD44 protein interacts with TGF-β receptor I, and enhance TGF-β1 signaling because the matrix metalloproteinase-9 (MMP-9), bounded with this complex, cleave pro-TGF-β1 into its active form 36 . At the same time in RCC (in Caki-1, Caki-2, ACHN, and 786-0) cells CD44 expression was shown to be up-regulated by Twist2 -member of the basic helix-loop-helix (bHLH) family 40 . In breast cancer model it has been shown that HIF-1α as a regulator of CD44 that increased the number of CD44 molecules and the percentage of (variant exons v6 and v7/8) CD44 positive cells is higher in cancer cells in hypoxia 41 , which might also be true for RCC that is known to harbor VHL mutations.…”

Section: Discussionmentioning

confidence: 95%

Renal carcinoma CD105−/CD44− cells display stem-like properties in vitro and form aggressive tumors in vivo

Fiedorowicz

Khan

Strzemecki

et al. 2020

Sci Rep

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clear cell renal cell carcinoma (ccRcc) is the most common kidney cancer. prognosis for ccRcc is generally poor since it is largely resistant to chemo-and radiotherapy. Many studies suggested that cancer stem cells/tumor initiating cells (CSCs/TICs) are responsible for development of tumor, disease progression, aggressiveness, metastasis and drug resistance. However, tumorigenic potential of CSCs/ tics isolated from established Rcc cell lines-basic ccRcc research model-has never been investigated in vivo. CD105+, CD105−, CD44+ and CD44− as well as CD44−/CD105− CD44+/CD105+ and CD44−/ CD105+ cells were isolated from Caki-1 RCC cell line, confirming coexistence of multiple subpopulations of stem-related phenotype in stable cell line. Sorted cells were injected subcutaneously into noD SciD mice and tumor growth was monitored with MRi and pet/ct. tumor growth was observed after implantation of CD105+, CD44+, CD44−, CD44−/CD105+ and CD44−/CD105− but not CD105− or CD44+/CD105+. Implantation of CD44−/CD105− cells induced tumors that were characterized by longer T1 and distinct metabolic pattern than other tumors. All the tumors were characterized by low uptake of [18F]FDG. CD105+ and CD44− tumors expresses Nanog and Oct-4, while CD44− tumors additionally expressed endothelial cell marker-CD31. Renal cell carcinoma (RCC), is the 10th malignancy worldwide and the most frequent type of kidney cancer in adults. Each year in Europe approximately 88 400 patients are diagnosed with RCC; the incidence and mortality of RCC are rising at a rate of 2-3% per decade, therefore novel therapies directed against RCC are needed. At the same time despite advancements in diagnostic techniques, up to 30% of newly diagnosed patients already present with metastases, and a large portion of patients that undergo surgical treatment experience the RCC recurrence, therefore drugs targeted against metastasis initiating cells would be of great interest in the future 1,2. Cancer stem cells (CSCs) are characterized by the potential to self-renew, high tumorigenicity in nude mice and the ability to efficiently reconstitute all tumor subpopulations and primary tumor phenotype 3-5. CSCs are also responsible not only for cancer development, but also for disease recurrence, progression and metastatic spread, together with cancer aggressiveness, including treatment resistance such as chemo/radiotherapy, and targeted treatment 6,7 , therefore basic research with careful model selection to understand their biology is mandatory to define novel potential therapeutic targets for all RCC subtypes 8,9 .

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“…The above signaling pathways, particularly ECM-receptor interaction pathway, are closely related to the pathogenesis of VRL. The ECM-receptor interaction pathway plays a crucial role in breast cancer and kidney cancer [25,59], and miRNAs have been shown to regulate this pathway [60]. The KEGG pathway analysis showed substantial overlap among the signal transduction pathways of target gene sets involved in cancer transcriptional dysregulation pathway, proteoglycan, and cancer pathways, suggesting that these pathways may be closely related to cancers including VRL.…”

Section: Discussionmentioning

confidence: 99%

High-Throughput MicroRNA Profiling of Vitreoretinal Lymphoma: Vitreous and Serum MicroRNA Profiles Distinct from Uveitis

Minezaki

Usui

Asakage

et al. 2020

JCM

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Purpose: Vitreoretinal lymphoma (VRL) is a non-Hodgkin lymphoma of the diffuse large B cell type (DLBCL), which is an aggressive cancer causing central nervous system related mortality. The pathogenesis of VRL is largely unknown. The role of microRNAs (miRNAs) has recently acquired remarkable importance in the pathogenesis of many diseases including cancers. Furthermore, miRNAs have shown promise as diagnostic and prognostic markers of cancers. In this study, we aimed to identify differentially expressed miRNAs and pathways in the vitreous and serum of patients with VRL and to investigate the pathogenesis of the disease. Materials and Methods: Vitreous and serum samples were obtained from 14 patients with VRL and from controls comprising 40 patients with uveitis, 12 with macular hole, 14 with epiretinal membrane, 12 healthy individuals. The expression levels of 2565 miRNAs in serum and vitreous samples were analyzed. Results: Expression of the miRNAs correlated significantly with the extracellular matrix (ECM) ‒receptor interaction pathway in VRL. Analyses showed that miR-326 was a key driver of B-cell proliferation, and miR-6513-3p could discriminate VRL from uveitis. MiR-1236-3p correlated with vitreous interleukin (IL)-10 concentrations. Machine learning analysis identified miR-361-3p expression as a discriminator between VRL and uveitis. Conclusions: Our findings demonstrate that aberrant microRNA expression in VRL may affect the expression of genes in a variety of cancer-related pathways. The altered serum miRNAs may discriminate VRL from uveitis, and serum miR-6513-3p has the potential to serve as an auxiliary tool for the diagnosis of VRL.

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Twist2 promotes kidney cancer cell proliferation and invasion by regulating ITGA6 and CD44 expression in the ECM-receptor interaction pathway

Cited by 46 publications

References 37 publications

Downregulation of HOXA3 in lung adenocarcinoma and its relevant molecular mechanism analysed by RT-qPCR, TCGA and in silico analysis

Downregulation of HOXA3 in lung adenocarcinoma and its relevant molecular mechanism analysed by RT-qPCR, TCGA and in silico analysis

Renal carcinoma CD105−/CD44− cells display stem-like properties in vitro and form aggressive tumors in vivo

High-Throughput MicroRNA Profiling of Vitreoretinal Lymphoma: Vitreous and Serum MicroRNA Profiles Distinct from Uveitis

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