Oncogene In Renal Cell Carcinoma Research Articles

Identification of miR‑195‑3p as an oncogene in RCC.

There is increasing evidence that the deregulation of microRNAs (miRNAs; miRs) contributes to tumorigenesis. Previous studies have shown that miR‑195 is downregulated in various types of cancer. The present study aimed to investigate the function and expression levels of miR‑125b. Results of qPCR revealed that miR‑195‑3p, the mature sequence of miR‑195, was upregulated in renal cell carcinoma (RCC) tissues and cell lines (786‑O, 769P and ACHN). This indicated that the function and role of miR‑195‑3p may differ in different types of tumor. To assess the function of miR‑195‑3p in RCC cell lines, cell proliferation was examined using MTT and CCK‑8 assays, mobility was assessed using a cell scratch assay, Transwell migration assay and invasion assay, and apoptosis was examined using flow cytometry. These assessments were also performed in cells with upregulated or downregulated miR‑195‑3p via transfection with synthesized miR‑195‑3p mimic or inhibitor. The results revealed that the overexpression of miR‑195‑3p promoted 786‑O and ACHN RCC cell proliferation, migration and invasion, and inhibited cell apoptosis, whereas the downregulation of miR‑195‑3p suppressed cell proliferation, migration and invasion, and induced cell apoptosis. These results indicated that miR‑195‑3p was associated with the tumorigenesis of RCC, with further investigations to focus on the pathway and use of miR‑195‑3p as a clinical biomarker for RCC.

MiR‑15a‑5p acts as an oncogene in renal cell carcinoma.

miRNAs have been reported to be involved in multiple cellular processes and the tumorigenesis of various cancers. miR‑15a‑5p (also termed miR‑15a) has previously been determined to be upregulated in renal cell carcinoma (RCC) by microarray profile. However, the expression and function of miR‑15a‑5p in RCC remain to be validated. In the present study, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to detect the expression levels of miR‑15a‑5p in RCC tissues and cells. The expression level of miR‑15a‑5p was upregulated or downregulated by transfecting synthesized miR‑15a‑5p mimics or inhibitors. The MTT assay, CCK‑8 assay, Transwell assay, wound healing assay, Hoechest33342 staining and flow cytometry were conducted to investigate the role of miR‑15a‑5p in RCC. The results of the RT‑qPCR demonstrated that miR‑15a‑5p was upregulated in RCC tissues and ACHN, 786‑O and 769P RCC cells compared with paired normal tissues and HEK‑293T cells. miR‑15a‑5p was observed to be associated with RCC cell proliferation, migration, invasion and apoptosis. The results demonstrated that miR‑15a‑5p may be important as a tumor promoter in RCC. To the best of our knowledge, the present study is the first to describe miR‑15a‑5p as a tumor promoter in RCC. Further research will be performed to investigate the underlying signaling pathway of miR‑15a‑5p and the potential role of miR‑15a‑5p as a biomarker for early detection, prognosis prediction and a therapeutic target of RCC.

Identification of long-non coding RNA UCA1 as an oncogene in renal cell carcinoma

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, which is associated with poor prognosis and high recurrence. Long non‑coding RNAs (lncRNAs) have been reported to be dysregulated in cancer and to be important in the regulation of carcinogenesis, thus suggesting that this class of molecules may be used as biomarkers in cancer. The lncRNA urothelial carcinoma associated 1 (UCA1) has been observed to be upregulated and to function as an oncogene in certain types of cancer; however, the role of UCA1 in RCC remains to be elucidated. The present study aimed to determine the expression and function of UCA1 in RCC. Quantitative polymerase chain reaction (qPCR) was used to determine the expression levels of UCA1 in 46 paired RCC and adjacent normal tissue samples. Furthermore, qPCR was used to determine the expression levels of UCA1 in four RCC cell lines compared with the human embryonic kidney 293T cell line. The impact of UCA1 on cell migration, proliferation and apoptosis was investigated by wound scratch assay, MTT and flow cytometry, respectively. The results of the present study demonstrated that UCA1 expression levels were significantly increased in RCC tissues and cells, as compared with the controls. Ectopic expression and gene silencing of UCA1 in RCC cell lines exerted opposite effects on cellular proliferation, migration and apoptosis, and the results suggested that UCA1 may function as an oncogene in RCC. These results indicated that UCA1 may be considered as a promising biomarker for diagnosis, and a therapeutic target in RCC. Further research is required to elucidate the role and target genes of UCA1 in RCC.

Oncogenic cAMP responsive element binding protein 1 is overexpressed upon loss of tumor suppressive miR-10b-5p and miR-363-3p in renal cancer.

Renal cell carcinoma (RCC) is the most common kidney cancer in adults and has a poor prognosis. cAMP responsive element binding protein 1 (CREB1) is a proto‑oncogenic transcription factor involved in malignancies of various organs. However, its functional role(s) have not yet been elucidated in RCC. We investigated the expression pattern, function and regulation of CREB1 in RCC. CREB1 was overexpressed in the RCC tissues and cell lines. Downregulation of CREB1 inhibited RCC tumorigenesis by affecting cell proliferation, migration and apoptosis. Multiple computational algorithms predicted that the 3'‑untranslated region (3'‑UTR) of human CREB1 mRNA is a target for miR‑10b‑5p and miR‑363‑3p. Luciferase reporter assay, qPCR and western blot analysis confirmed that miR‑10b‑5p and miR‑363‑3p bind directly to the 3'‑UTR of CREB1 mRNA and inhibit mRNA and protein expression of CREB1. qPCR data also revealed a significantly lower expression of miR‑10b‑5p and miR‑363‑3p in RCC tissues. Introduction of miR‑10b‑5p and miR‑363‑3p mimics led to suppressed expression of CREB1 and inhibited cell proliferation, migration and apoptosis reduction. Taken together, we propose that CREB1 is an oncogene in RCC and that upregulation of CREB1 by loss of tumor suppressive miR‑10b‑5p and miR‑363‑3p plays an important role in the tumorigenesis of RCC.

MiR-630 functions as a tumor oncogene in renal cell carcinoma.

IntroductionMicroRNAs (miRNAs) are non-coding RNAs that regulate multiple cell processes during cancer progression. Renal cell carcinoma (RCC) is a malignancy with a poor prognosis. In this study, we aimed to investigate the roles of miR-630 in RCC progression.Material and methodsExpression of miR-630 was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) in four renal cancer cell lines (786-O, ACHN, Caki-1, and Caki-2) and one normal human proximal tubule epithelial cell line (HK-2). Next, miR-630 inhibitor was used to inhibit miR-630 expression in 786-O cells. Finally, its effects on cell proliferation, apoptosis, migration, and invasion were evaluated.ResultsThe expression level of miR-630 was higher in renal cancer cell lines 786-O, ACHN, Caki-1, and Caki-2 than that in the normal renal cell line HK-2 (p < 0.05). Furthermore, a proliferation assay, apoptosis assay, migration assay and invasion assay were performed, and the results showed that down-regulation of miR-630 expression by miR-630 inhibitor significantly inhibited cell proliferation, migration, and invasion, which meanwhile induced cell apoptosis of the renal cancer cell line 786-O.ConclusionsThis is the first time that miR-630 expression has been shown to be associated with renal cancer progression, and down-regulation of miR-630 can inhibit tumor progression, which provides a potential therapeutic target for renal cancer treatment.

Identification of miR‑130b as an oncogene in renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common type of renal tumor, which has a poor prognosis. Improvements in understanding the underlying molecular biology of RCC has led to systemic treatments, which have markedly improved patient outcomes. Therefore, it is necessary and worthwhile to identify novel biomarkers for RCC. MicroRNAs (miRNAs) have been found to be important in a wide range of biological and pathological processes, including cell differentiation, migration, growth, proliferation, apoptosis and metabolism. Aberrant expression of miRNA‑130b has previously been reported in tumors, however, its role in RCC remains to be elucidated. In the present study, the upregulation of miR‑130b was observed in RCC tissues and cell lines using reverse transcription‑quantitative polymerase chain reaction analysis, which was consistent with previous microRNA profiling in RCC. Furthermore, the effects of miR‑130b on cell migration, proliferation and apoptosis were examined using a wound scratch assay, an MTT assay and flow cytometric analysis, respectively. The results demonstrated that the downregulation of miR‑130b by a synthesized inhibitor inhibited cell migration, suppressed cell proliferation and induced RCC cell apoptosis. The present study was the first, to the best of our knowledge, to suggest that miR‑130b may be a promising biomarker for diagnosis and a therapeutic target for the treatment of RCC. Further investigations are required to examine the roles and target genes of miR‑130b in RCC.

MicroRNA-106b functions as an oncogene in renal cell carcinoma by affecting cell proliferation, migration and apoptosis.

Kidney cancer is the 14th most common cancer in the world and its prognosis remains poor due to difficult early detection and treatment. Therefore, the identification of biomarkers for early-stage renal cell carcinoma (RCC) is important. MicroRNA-106b (miR-106b) has been described as an oncogene in several types of human cancer. Previous microarray studies have suggested that miR-106b was significantly upregulated in RCC tissues compared with paired normal kidney tissues and may be a promising biomarker for the prediction of early metastasis following nephrectomy. The present study aimed to determine the expression and function of miR-106b in RCC. The expression of miR-106b in RCC tissues and cells, and in paired normal tissues and cells was determined by reverse transcription quantitative polymerase chain reaction, based on the previous sequencing results of miRNAs. Furthermore, a wound scratch assay, MTT assay and flow cytometry were performed to examine the functions of miR-106b on cell migration, proliferation and apoptosis. The results demonstrated that miR-106b was upregulated in RCC tissues and cell lines compared with control normal tissues and cell lines. Downregulation of miR-106b with a synthesized inhibitor suppressed cell migration and proliferation and induced renal cancer cell apoptosis, suggesting that miR-106b can be characterized as an oncogene in RCC. To the best of our knowledge, the present study was the first to reveal that miR-106b is upregulated and affects cellular migration, proliferation and apoptosis in RCC. Further studies are required to examine the role and target genes of miR-106b in RCC.

MicroRNA-509-3p inhibits cancer cell proliferation and migration by targeting the mitogen-activated protein kinase kinase kinase 8 oncogene in renal cell carcinoma.

microRNAs (miRNAs; miR) are a class of small non-coding RNA molecules, which are involved in the pathogenesis of human diseases through the negative regulation of gene expression. Previous studies have demonstrated that miR-509-3p is a novel miRNA associated with cell proliferation and migration in 786-O renal cell carcinoma (RCC) cells. However, the mechanism of action of miR-509-3p in RCC remains to be elucidated. The present study aimed to examine the functional role and mechanism of miR-509-3p in the development of RCC. The results demonstrated that the expression levels of miR-509-3p were downregulated in the 786-O and ACHN RCC cell lines compared with the normal tissues of 10 patients with RCC, as determined by reverse transcription-quantitative polymerase chain reaction. The mRNA expression levels of mitogen-activated protein kinase kinase kinase 8 (MAP3K8) were upregulated in the RCC cell lines. Functional investigations demonstrated that the overexpression of miR-509-3p inhibited the migration and proliferation of the RCC cells, as determined by wound scratch and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Luciferase reporter assays revealed that the overexpression of miR-509-3p reduced the transcriptional activity of MAP3K8. Furthermore, the present study demonstrated that the ectopic transfection of miR-509-3p led to a significant reduction in the mRNA and protein expression levels of MAP3K8 in the RCC cells. Finally, knockdown of MAP3K8 inhibited the migration and proliferation of the RCC cells. Therefore, the results of the present study demonstrated that the miR-509-3p RCC suppressor was a significant regulator of the MAP3K8 oncogene, suggesting that it may have a potential therapeutic role in the treatment of RCC.

Identification of miR-7 as an oncogene in renal cell carcinoma

MicroRNA-7 (miR-7) has been described as a tumor suppressor in several human cancers, but the results of a study to identify miRNAs associated with metastatic capability in breast cancer suggested that miR-7 may be characterized as an oncogene. The present study was to determine the expression and function of miR-7 in renal cell carcinoma. Quantitative real-time polymerase chain reaction was used to validate the expressions of miR-7 in 48 paired renal cell carcinomas (RCC) and normal tissues, based on the preliminary sequencing results of miRNAs. Furthermore, the impacts of miR-7 on cell migration, proliferation and apoptosis were analyzed using wound scratch assay, MTT and flow cytometry, respectively. The results demonstrated that miR-7 was up-regulated in RCC compared with normal tissues (p = 0.001). Down-regulation of miR-7 with synthesized inhibitor inhibited cell migration in vitro, suppressed cell proliferation and induced renal cancer cell apoptosis, prompting that miR-7 could be characterized as an oncogene in RCC. The present study was the first to reveal that miR-7 was up-regulated in RCC and it played an important role in RCC by affecting cellular migration, proliferation and apoptosis. Further researches should be conducted to explore the roles and target genes of miR-7 in RCC and other cancers.

Knockdown of clusterin inhibits the growth and migration of renal carcinoma cells and leads to differential gene expression

Clusterin (CLU) is a glycoprotein involved in tumor progression, whose expression level correlates with the metastasis of renal cell carcinoma (RCC). However, the mechanism by which CLU plays an oncogenic role in RCC remains unclear. In this study, we used the human renal cancer cell786-O as an experimental model. We knocked down CLU expression in the 786-Ocells using lentiviral vector-mediated delivery of RNAi, and then compared the gene expression profiles between the knocked down CLU 786-Ocells and control cells. We observed that CLU knockdown induced apoptosis and inhibited the proliferation and migration of 786-Ocells. Microassay analysis revealed changes in the expression of 588genes between the 786-Ocells infected by a si-CLU lentivirus and the control cells, where 356genes were upregulated and 232were downregulated. Pathway analysis classified the differentially expressed genes into 17upregulated and 12downregulated pathways, including the PI3K/Akt, MAPK and VEGF pathways. In this study, we demonstrated that CLU acts as an oncogene in RCC by promoting cell proliferation and migration and inhibiting apoptosis. Microassay analysis may provide a platform for further characterization of the individual genes implicated in the development of RCC, providing new insights into the oncogenic role of CLU.

Upregulated microRNA-16 as an oncogene in renal cell carcinoma.

MicroRNAs (miRs) are small, endogenous noncoding RNAs that serve a significant function in various biologic processes, including those involved in cancer. The present study aimed to determine the expression and function of miR-16 in renal cell carcinoma (RCC). Quantitative polymerase chain reaction was used to quantify the expression of miR-16 in 48 paired RCC tissues and adjacent normal tissues. The impact of miR-16 on cell proliferation, migration and apoptosis was analyzed by transfecting miR-16 mature molecules into the renal cancer cell lines 786-O and ACHN. The results indicated that miR-16 was significantly upregulated in RCC tissues (P<0.05). Downregulation of miR-16 resulted in reduced cell proliferation and migration and increased levels of apoptosis, while overexpression of miR-16 resulted in accelerated cellular proliferation and migration, suggesting that miR-16 may function as an oncogene in RCC. The present study demonstrated for the first time, to the best of our knowledge, that miR-16 is upregulated in RCC and acts as an oncogene by inducing cellular proliferation, migration and reducing apoptosis. Further study of miR-16 in RCC may clarify the molecular mechanisms of RCC carcinogenesis and aid in the development of novel biomarkers and therapeutic options.

Higher expression of K-ras is associated with parathyroid hormone-related protein-induced hypercalcaemia in renal cell carcinoma.

To determine whether the K-ras oncogene is associated with parathyroid hormone-related protein (PTHrP) production in renal cell carcinoma (RCC) and whether the serum value of PTHrP is related to the patients' survival. The serum levels of PTHrP and corrected serum calcium levels were analysed in 51 consecutive patients (29 men and 22 women, mean age 63.7 years, range 33-82) with newly diagnosed RCC. Matched pairs were analysed of the mRNA levels of K-ras and PTHrP in tumour and in corresponding non-tumour tissue originating from the same patient, using the polymerase chain reaction after reverse transcription. Seven patients had elevated serum PTHrP values at the diagnosis of RCC. The mRNA expression of K-ras and PTHrP were detected in both tumour and non-tumour tissues, with K-ras mRNA levels being higher in the former than the latter (P < 0.05), and correlated with tumour stage (P < 0.05). There were no differences in PTHrP mRNA levels between the tissues. Furthermore, the mRNA levels of K-ras and PTHrP in seven tumours from patients with high serum values of PTHrP were higher than in tumours from those with normal values (both P < 0.01). The expression of mRNAs of K-ras and PTHrP was positively correlated (r = 0.771, P < 0.001). In seven patients with high serum PTHrP values the mRNA levels of PTHrP correlated with serum values of PTHrP and calcium (r = 0.875, P < 0.01 and r = 0.762, P < 0.05, respectively). Kaplan-Meier plots of survival rate in patients with elevated or normal serum PTHrP showed that high serum PTHrP was associated with a shorter overall survival (P < 0.05). The Cox proportional hazards model showed that serum PTHrP was an independent predictor of overall survival (P < 0.05). These findings suggest that K-ras may be associated with PTHrP-induced hypercalcaemia and that PTHrP levels may reflect the aggressiveness of tumour cells through the K-ras oncogene in RCC.