A Comprehensive Analysis of PAX8 Expression in Human Epithelial Tumors

Renal cell carcinoma (RCC) is arguably the deadliest form of genitourinary malignancy and is nowadays viewed as a heterogeneous series of cancers, with the same origin but fundamentally different metabolisms and clinical behaviors. Immunohistochemistry (IHC) is increasingly necessary for RCC subtyping and definitive diagnosis. WT1 is a complex gene involved in carcinogenesis. To address reporting heterogeneity and WT1 IHC standardization, we used a recent N-terminus targeted monoclonal antibody (clone WT49) to evaluate WT1 protein expression in 56 adult RCC (aRCC) cases. This is the largest WT1 IHC investigation focusing exclusively on aRCCs and the first report on clone WT49 staining in aRCCs. We found seven (12.5%) positive cases, all clear cell RCCs, showing exclusively nuclear staining for WT1. We did not disregard cytoplasmic staining in any of the negative cases. Extratumoral fibroblasts, connecting tubules and intratumoral endothelial cells showed the same exclusively nuclear WT1 staining pattern. We reviewed WT1 expression patterns in aRCCs and the possible explanatory underlying metabolomics. For now, WT1 protein expression in aRCCs is insufficiently investigated, with significant discrepancies in the little data reported. Emerging WT1-targeted RCC immunotherapy will require adequate case selection and sustained efforts to standardize the quantification of tumor-associated antigens for aRCC and its many subtypes.

Human leukocyte alpha-interferon (IFN-alpha) has significant antitumor activity in advanced renal cell carcinoma (RC), with approximately 15% (range, 5 to 29%) of patients subjected to IFN-alpha therapy exhibiting a major objective response. We assayed 16 RC cell lines for intrinsic sensitivity to the growth-inhibitory effects of recombinant IFN-alpha. Similar to results observed in patients, cultured RCs could be divided into those that are inhibited by IFN-alpha and those that are not. In addition, the IFN-alpha-sensitive or -resistant phenotype of cultured RCs was correlated with surface expression of six unrelated kidney-associated differentiation antigens. The expression of one antigen, a Mr 160,000 glycoprotein (gp160), was found to correlate with resistance to IFN-alpha. Proliferation of seven RC cell lines expressing gp160 (gp160+) was not significantly inhibited by IFN-alpha at concentrations as high as 3000 units/ml. In contrast, proliferation of eight of nine RC cell lines lacking expression of gp160 (gp160-) was markedly inhibited by IFN-alpha. The effect of IFN-alpha on gp160+ and gp160- RC xenografts in nu/nu mice was examined. In separate experiments, two gp160+ RC cell lines and five gp160- RC cell lines were injected s.c. into nu/nu mice; one half of the mice were subsequently treated with 10(6) units of IFN-alpha i.p. 3 times a wk, and one half received no IFN-alpha. Tumors appeared at the sites of inoculation in all mice given injections of gp160+ RC cell lines within 10 to 25 days regardless of INF-alpha therapy. Mice given injections of gp160- RC cell lines, but not receiving IFN-alpha, also formed tumors. In contrast, gp160- RC cell lines injected into mice that were treated with IFN-alpha exhibited a marked sensitivity, as demonstrated by either no tumor formation or delayed tumor formation. We conclude that the absence of gp160 expression by RCs may be predictive of sensitivity to the antitumor effects of IFN-alpha and, thus, provide a basis for identifying IFN-responsive patients.

<div>Abstract<p>Following treatment with a demethylating agent, 5 of 11 renal cell carcinoma (RCC) cell lines showed increased expression of hepatocyte growth factor (HGF) activator inhibitor type 2 (HAI-2/SPINT2/Bikunin), a Kunitz-type protease inhibitor that regulates HGF activity. As activating mutations in the <i>MET</i> proto-oncogene (the HGF receptor) cause familial RCC, we investigated whether <i>HAI-2/SPINT2</i> might act as a RCC tumor suppressor gene. We found that transcriptional silencing of <i>HAI-2</i> in RCC cell lines was associated with promoter region methylation and HAI-2/SPINT2 protein expression was down-regulated in 30% of sporadic RCC. Furthermore, methylation-specific PCR analysis revealed promoter region methylation in 30% (19 of 64) of clear cell RCC and 40% (15 of 38) of papillary RCC, whereas mutation analysis (in 39 RCC cell lines and primary tumors) revealed a missense substitution (P111S) in one RCC cell line. Restoration of HAI-2/SPINT2 expression in a RCC cell line reduced <i>in vitro</i> colony formation, but the P111S mutant had no significant effect. Increased cell motility associated with HAI-2/SPINT2 inactivation was abrogated by treatment with extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phospholipase C-γ inhibitors, but not by an inhibitor of atypical protein kinase C. These findings are consistent with frequent epigenetic inactivation of <i>HAI-2/SPINT2</i>, causing loss of RCC tumor suppressor activity and implicate abnormalities of the MET pathway in clear cell and papillary sporadic RCC. This information provides opportunities to develop novel targeted approaches to the treatment of RCC.</p></div>

Following treatment with a demethylating agent, 5 of 11 renal cell carcinoma (RCC) cell lines showed increased expression of hepatocyte growth factor (HGF) activator inhibitor type 2 (HAI-2/SPINT2/Bikunin), a Kunitz-type protease inhibitor that regulates HGF activity. As activating mutations in the MET proto-oncogene (the HGF receptor) cause familial RCC, we investigated whether HAI-2/SPINT2 might act as a RCC tumor suppressor gene. We found that transcriptional silencing of HAI-2 in RCC cell lines was associated with promoter region methylation and HAI-2/SPINT2 protein expression was down-regulated in 30% of sporadic RCC. Furthermore, methylation-specific PCR analysis revealed promoter region methylation in 30% (19 of 64) of clear cell RCC and 40% (15 of 38) of papillary RCC, whereas mutation analysis (in 39 RCC cell lines and primary tumors) revealed a missense substitution (P111S) in one RCC cell line. Restoration of HAI-2/SPINT2 expression in a RCC cell line reduced in vitro colony formation, but the P111S mutant had no significant effect. Increased cell motility associated with HAI-2/SPINT2 inactivation was abrogated by treatment with extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phospholipase C-gamma inhibitors, but not by an inhibitor of atypical protein kinase C. These findings are consistent with frequent epigenetic inactivation of HAI-2/SPINT2, causing loss of RCC tumor suppressor activity and implicate abnormalities of the MET pathway in clear cell and papillary sporadic RCC. This information provides opportunities to develop novel targeted approaches to the treatment of RCC.

<div>Abstract<p>Following treatment with a demethylating agent, 5 of 11 renal cell carcinoma (RCC) cell lines showed increased expression of hepatocyte growth factor (HGF) activator inhibitor type 2 (HAI-2/SPINT2/Bikunin), a Kunitz-type protease inhibitor that regulates HGF activity. As activating mutations in the <i>MET</i> proto-oncogene (the HGF receptor) cause familial RCC, we investigated whether <i>HAI-2/SPINT2</i> might act as a RCC tumor suppressor gene. We found that transcriptional silencing of <i>HAI-2</i> in RCC cell lines was associated with promoter region methylation and HAI-2/SPINT2 protein expression was down-regulated in 30% of sporadic RCC. Furthermore, methylation-specific PCR analysis revealed promoter region methylation in 30% (19 of 64) of clear cell RCC and 40% (15 of 38) of papillary RCC, whereas mutation analysis (in 39 RCC cell lines and primary tumors) revealed a missense substitution (P111S) in one RCC cell line. Restoration of HAI-2/SPINT2 expression in a RCC cell line reduced <i>in vitro</i> colony formation, but the P111S mutant had no significant effect. Increased cell motility associated with HAI-2/SPINT2 inactivation was abrogated by treatment with extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phospholipase C-γ inhibitors, but not by an inhibitor of atypical protein kinase C. These findings are consistent with frequent epigenetic inactivation of <i>HAI-2/SPINT2</i>, causing loss of RCC tumor suppressor activity and implicate abnormalities of the MET pathway in clear cell and papillary sporadic RCC. This information provides opportunities to develop novel targeted approaches to the treatment of RCC.</p></div>

Interleukin-6 (IL-6) is produced at high levels by renal cell carcinoma cell lines. The molecular mechanisms involved in its possible role as an autocrine growth factor were investigated. IL-6 and IL-6 receptor expression was investigated in 8 renal cell carcinoma (RCC) cell lines. The modulation of RCC cell line proliferation by an anti-IL-6 Ab, an IL-6 antisense oligonucleotide (ASON) directed against the second exon of IL-6 and cytokines inhibiting IL-6 production (IL-4 and IL-13) was investigated. All 8 RCC cell lines expressed IL-6 mRNA, produced IL-6 and expressed the soluble and membrane-bound gp130 chain of IL-6 receptor. The gp80 chain of IL-6 receptor was undetectable at the surface of the 8 RCC cell lines tested, while the soluble form of gp80 was detectable in the supernatant of one of these cell lines. The addition of a blocking IL-6 Ab did not inhibit the proliferation of any of the 8 RCC cell lines. In contrast, IL-6 ASON inhibited specifically IL-6 production and the proliferation of all RCC cell lines. Exogenous IL-6 failed to restore RCC cell line proliferation blocked by ASON, indicating that IL-6 acts through an intracrine loop in RCC cell lines. IL-13 and IL-4 inhibited the proliferation of 7 of the 8 cell lines without interfering with IL-6 or IL-6 receptor expression. IL-6 ASON inhibited the proliferation of the 8 RCC cell lines tested additively with IL-4 or IL-13. IL-6 is an intracrine growth factor in renal cell carcinoma cell lines.

Expression of Pax2 in Human Renal Tumor-Derived Endothelial Cells Sustains Apoptosis Resistance and Angiogenesis

Renal cell carcinoma (RCC) is the most common type of kidney cancer with rising incidence. Long noncoding RNA (lncRNA) LINC01133 is a novel lncRNA that is involved in the development of several types of cancers. However, the role of LINC01133 in RCC has not been reported. Thus, in this study, we investigated the functions of LINC01133 in RCC. The qualitative real-time polymerase chain reaction analysis was performed to examine the levels of LINC01133 in RCC tissues and adjacent tissues, as well as RCC cell lines. The results showed that LINC01133 was highly expressed in RCC tissue specimens and cell lines. Downregulation of LINC01133 significantly inhibited the proliferation, migration, and invasion of RCC cells. Further mechanistic investigations proved that LINC01133 directly interacted with microRNA (miR)-30b-5p and regulated the miR-30b-5p expression in RCC cell lines. Moreover, miR-30b-5p exhibited tumor-suppressive activity in RCC cell lines, which was mediated by targeting Ras-related protein Rab-3D (Rab3D). In vivo study showed that LINC01133 knockdown suppressed tumor growth in the nude mice. Taken together, these findings indicated that LINC01133 might be an oncogene in RCC through regulation of the miR-30b-5p/Rab3D axis. Thus, LINC01133 might serve as a potential therapeutic target for the treatment of RCC.

Renal cell carcinoma (RCC) is the most common form of kidney cancer, consisting of multiple distinct subtypes. RCC has the highest mortality rate amongst the urogenital cancers, with kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and kidney chromophobe carcinoma (KICH) being the most common subtypes. The Paired-box (PAX) gene family encodes transcription factors, which orchestrate multiple processes in cell lineage determination during embryonic development and organogenesis. Several PAX genes have been shown to be expressed in RCC following its onset and progression. Here, we performed real-time quantitative polymerase chain reaction (RT-qPCR) analysis on a series of human RCC cell lines, revealing significant co-expression of PAX2, PAX6, and PAX8. Knockdown of PAX2 or PAX8 mRNA expression using RNA interference (RNAi) in the A498 RCC cell line resulted in inhibition of cell proliferation, which aligns with our previous research, although no reduction in cell proliferation was observed using a PAX2 small interfering RNA (siRNA). We downloaded publicly available RNA-sequencing data and clinical histories of RCC patients from The Cancer Genome Atlas (TCGA) database. Based on the expression levels of PAX2, PAX6, and PAX8, RCC patients were categorized into two PAX expression subtypes, PAXClusterA and PAXClusterB, exhibiting significant differences in clinical characteristics. We found that the PAXClusterA expression subgroup was associated with favorable clinical outcomes and better overall survival. These findings provide novel insights into the association between PAX gene expression levels and clinical outcomes in RCC patients, potentially contributing to improved treatment strategies for RCC.

To examine the significance of the methylation level of the p53 target and tumour suppressor genes apoptotic protease activating factor-1 (APAF-1) and death-associated protein kinase-1 (DAPK-1) in 80 microdissected tumour samples from transitional cell carcinoma (TCC) of the bladder and 80 tumour samples from clear-cell renal cell carcinoma (RCC) as well as from non-tumourous bladder and kidney tissue. Growth-inhibitory effects of the demethylating agents 5-Aza-2′-deoxycytidine (5-Aza-CdR) and zebularine were investigated in TCC and RCC cell lines. The methylation frequency of APAF-1 (DAPK-1) was 100% (77%) in TCC and 100% (33%) in RCC. The methylation levels of APAF-1 could differentiate between the individual tumour stages in TCC as well as in RCC. The APAF-1 methylation levels in RCC were significantly higher in tumours larger than 4 cm and in high-grade tumours. The methylation frequencies in normal tissue for APAF-1 (DAPK-1) were 11% (8%) in bladder tissue and 9% (5%) in kidney tissue. The growth-inhibitory effect of the demethylating agents in TCC (RT4, T24) and RCC (A498, ClearCa-5) cell lines resulted in a 17–132% prolongation of the doubling time (DT). In RCC cell lines, zebularine was superior to 5-Aza-CdR in achieving a DT prolongation. Quantitative real time RT-PCR detected a re-expression of mRNA transcripts of APAF-1 or DAPK-1. In conclusion, demethylating agents effectively retard growth of TCC and RCC cell lines. Methylation level analysis of specific genes has the potential for further tumour characterisation in TCC and RCC.

ObjectiveRenal cell carcinoma (RCC) displays an increasing incidence and mortality rate worldwide in recent years. More and more evidence demonstrated microRNAs function as positive or negative regulatory factors in many cancers, while the role of miR-301a in RCC is still unclear.Material and MethodsThe expression and clinical significance of miR-301a were assessed via bioinformatic software on open microarray datasets of the Cancer Genome Atlas (TCGA) and then confirmed by quantitative real-time PCR (qRT-PCR) in RCC cell lines. Loss of function assays were performed in RCC cell lines both in vitro and in vivo. Cell Counting Kit-8 (CCK-8), flow cytometry, luciferase reporter assays, Western blotting, and immunohistochemistry were employed to explore the mechanisms of the effect of miR-301a on RCC.ResultsBy analyzing RCC clinical specimens and cell lines, we found a uniform increased miR-301a in expression in comparison with normal renal tissue or normal human proximal tubule epithelial cell line (HK-2). In addition, miR-301a upregulation correlated advanced stage and poor prognosis of clear cell RCC (ccRCC). Anti-miR-301a could inhibit growth and cell cycle G1/S transition in RCC cell lines. Moreover, we found that PTEN was identified as a direct target of miR-301a that might partially interrupt miR-301a-induced G1/S transition. Importantly, nude-mouse models revealed that knockdown of miR-301a delayed tumor growth.ConclusionThese results indicate that miR-301a functions as a tumor-promoting miRNA through regulating PTEN expression, representing a novel therapeutic target for RCC.

To provide the basis for improved therapeutic benefit in combination chemotherapy with interferon (IFN) and 5-fluorouracil (5-FU), we investigated the modulatory actions of human recombinant IFN alfa-2a on 5-FU in five renal cell carcinoma (RCC) cell lines in vitro, in particular focusing on thymidine phosphorylase (TP) expression. The sensitivity of RCC cell lines to the drugs was evaluated using an AlamarBlue assay. An enzyme-linked immunosorbent assay (ELISA) was used to determine TP expression. IFN-alpha enhanced the sensitivity of three of five RCC cell lines to 5-FU in a dose- and schedule-dependent manner. When IFN-alpha was given prior to 5-FU, sensitivity to 5-FU was significantly higher than when IFN-alpha was given simultaneously (P < 0.05). IFN-alpha enhanced TP expression in a dose-dependent manner in three of five RCC cell lines (P < 0.05). The relative IFN-alpha-induced increase in sensitivity to 5-FU correlated with the relative IFN-alpha-induced increase in TP expression (P < 0.05). In addition, two of three RCC cell lines with more than a twofold increase in sensitivity to 5-FU induced by IFN-alpha showed a higher TP expression without IFN-alpha stimulation. These results suggest that IFN-alpha upregulates TP expression and modulates 5-FU anabolism thus enhancing 5-FU cytotoxicity in a dose- and schedule-dependent manner in some RCC cells. The results imply that TP expression measurement in RCC could identify subgroups of metastatic RCC that may respond to IFN-alpha/5-FU combination therapy, and sequential administration of IFN-alpha followed by 5-FU may be beneficial in such cases.

PurposemicroRNAs are thought to play crucial roles in tumorigenesis. Dysregulation of miR-488 has been implicated to be involved in several cancer progressions. However, the biological functions of miR-488 in renal cell carcinoma (RCC) remain unclear. This study aimed to explore the molecular mechanism underlying the role of miR-488 in RCC development.Materials and methodsThe expression levels of miR-488 were detected in 38 paired RCC tumor samples and cell lines by quantitative real-time polymerase chain reaction method. miR-488 was upregulated by mimics transfection in RCC cell lines. MTT, colony formation, transwell assay, flow cytometry assay, and a xenograft model were performed to determine cell proliferation, invasion, migration, epithelial-to-mesenchymal transition, and apoptosis in vitro and in vivo. Moreover, the potential target of miR-488 was verified by dual-luciferase reporter assay, quantitative real-time polymerase chain reaction, and Western blot. The correlation between miR-488 expression and its target gene expression was confirmed by Spearman’s correlation analysis in 38 selected RCC tissue samples.ResultsWe found that miR-488 was remarkably downregulated in human RCC samples and cell lines compared with paired normal tissues and cell lines. Functional investigations revealed that overexpression of miR-488 significantly suppressed cell proliferation, invasion, and migration, and promoted cell apoptosis in RCC cells. Nucleosome binding protein 1 (high-mobility group nucleosome binding domain 5 [HMGN5]) was identified as a direct target of miR-488, and an inverse relationship was found between miR-488 expression and HMGN5 mRNA levels in RCC specimens. Rescue experiments suggested that restoration of HMGN5 partially abolished miR-488-mediated cell proliferation and invasion inhibition in RCC cells through regulating phosphatidylinositol 3-kinase/protein kinase B/the mammalian target of rapamycin and epithelial-to-mesenchymal transition signaling pathways.ConclusionThese data indicated that miR-488 acted as a tumor suppressor in RCC proliferation and invasion by targeting HMGN5, which might provide potential therapeutic biomarker for RCC patients.

Renal cell carcinomas (RCC) are highly metastatic and therapy-resistant. Several novel tyrosine kinase inhibitors (TKI) targeting angiogenesis have been introduced into clinical practice for RCC, the most common being sunitinib. However, use of sunitinib is limited by development of therapy resistance in RCC. Comprehensive characterisation of morphological, functional and molecular changes in sunitinib-resistant RCC cells is lacking. Understanding the mechanisms of resistance to sunitinib therapy, and developing measures to overcome resistance, may help improve patient care.The overall hypotheses of this project were: 1) that RCC models that demonstrate resistance to current RCC therapies can be utilised to investigate and define molecular pathways of resistance; and 2) that these same models can be used to test novel therapies. Specifically, the project aimed: 1) to develop and characterise RCC cell lines that are resistant to sunitinib; 2) to explore the mechanisms of resistance in the RCC cell lines with emphasis on angiogenic and apoptotic pathways; 3) to overcome sunitinib-resistance with appropriate agents using in vitro methodologies; and 4) to validate in vitro findings in a murine xenograft model of RCC.A literature review is provided in Chapter 1, and general Materials and Methods are described in Chapter 2. Chapters 3 describes development of sunitinib resistance in four human RCC cell lines: 786-0, Caki-1, Caki-2, and SN12K1 and characterise the differences in cell and molecular biology from parental RCC cell lines. The RCC cell lines were made resistant to continuous, chronic exposure to 10 μM sunitinib. Cell growth/proliferation (MTT assay), morphology and apoptosis (phase-contrast microscopy and hematoxylin-eosin staining), transmigration (migration chamber), and gene expression (qRT-PCR) for interleukin-6 and -8 (IL-6, IL-8), vascular endothelial growth factor (VEGF), Bcl2 and Bax were studied. Resistant cells were stable in 10 μM sunitinib, maintained viability in 20 μM sunitinib, and have now been in culture for over two years. Resistant cells proliferated more slowly, but were significantly hypertrophic compared with parental cells. The transmigration assay showed no difference between resistant cells and their respective parental cells. One of the most striking differences between resistant and parental RCC was that IL-6 (in all RCC) and IL-8 (in most RCC) significantly increased in resistant cells, with an associated increase in VEGF. An anti-apoptotic mechanism was also demonstrated in therapy-resistant RCC. Increased IL-6 may contribute to resistance of RCC through downstream upregulation VEGF.Thus, IL-6 increase was considered worthy of further investigation as a potential therapeutic target for therapy-resistant RCC. In Chapter 4, resistant cells were grown with and without Tocilizumab (50 μg/mL), a monoclonal antibody that blocks the IL-6 receptor (IL-6R) protein. Cell growth/proliferation, cell morphology and apoptosis, gene expression (qRT-PCR) and protein levels (ELISA) for IL-6, VEGF, Bcl2 and Bax were again studied. The in vitro results demonstrated that inhibition of IL-6R by Tocilizumab inhibited cell growth, increased apoptosis, decreased VEGF expression, and reactivated and retrieved the sunitinib sensitivity.Chapter 5 provides some preliminary data of a mouse preclinical model investigating the use of Tocilizumab in the sunitinib-resistant RCC cell lines. These were implanted sub-cutaneously in NOD-SCID immunodeficient mice (1.6 x 106 cells per 100 μL of PBS). The animals were randomly divided into four groups (N=6) of sunitinib-resistant cell lines. All mice in each group were injected subcutaneously with 100 μL of cell suspension. Viability of any remaining cells was verified after injection of animals, using a Trypan blue exclusion assay and regrowth in culture. Food and water intake, body weight and tumour growth were monitored throughout the experiment. One week after RCC injection, three mice from each group were injected with Tocilizumab (100 μg in 100 μL, three times per week for five weeks, intraperitoneal/IP injection). The other mice were given 100 μL IP physiological saline. After five weeks of Tocilizumab, mice were euthanased and tumours removed. Tumour weight was measured and tumour volume estimated. All organs were checked for metastatic clones of RCC, but none were detected. Tumour tissue was collected and frozen for RNA analysis. Fixed tumour and organ tissue was prepared for morphological analyses (microscopy; ApopTag for apoptosis), and immunohistochemistry for Ki67 (proliferation), IL-6 and VEGF. Only Caki-1 and SN12K1 RCC grew. Tocilizumab did not significantly decrease tumour weight in Caki-1 tumours, but there was a significant decrease in IL-6 and VEGF mRNA. Surprisingly, in SN12K1 tumours, there was a non-significant increase in mean tumour weight, and a significant increase in VEGF mRNA, with Tocilizumab.In the concluding Chapter (Chapter 6), a summary of major findings and future directions of this project are presented. Using the in vitro model, the project has confirmed that targeting IL-6 in therapy-resistant RCC could retrieve their susceptibility to cancer therapy. The significance of the project is that improving the understanding of RCC development and therapy resistance provides the exciting potential for testing personalised adjuvant therapies for treatment of RCC.

Renal cell carcinoma(RCC) is one of the third most common types of urological cancer worldwide. Long non‑coding RNA(lncRNA) ROR has been reported to be important in regulating the malignant activities of different types of cancer, however, the function of lncRNA ROR in RCC remains to be fully elucidated. In order to investigate the function of lncRNA ROR in RCC, reverse transcription‑quantitative polymerase chain reaction(RT‑qPCR) analysis was used to detect the expression of lncRNA ROR in renal cancer tissues and adjacent tissues. Cell proliferation and apoptosis were determined using Cell Counting Kit-8 and apoptosis assays. Western blot analysis was used to measure the expression levels of c‑Myc and p53 following the suppression of lncRNA ROR in RCC cell lines. According to the results of the RT‑qPCR analysis, lncRNA ROR was found to be expressed at high levels in RCC tissues and cell lines. Patients with RCC exhibiting high expression levels of lncRNA ROR had shorter survival rates, compared with those with low expression levels of lncRNA ROR. The knockdown of lncRNA ROR resulted in a decrease of cell proliferation and increase of apoptosis invitro. The suppression of lncRNA ROR also induced an increase in the expression of p53 and a decrease in the expression of c‑Myc invitro. Taken together, these results demonstrated that lncRNA ROR was expressed at high levels in RCC tissue and cell lines, and was associated with the proliferation ability of RCC cells. These findings indicate that lncRNA ROR may be a promising therapeutic target for treating RCC.