Long non-coding RNA MIR4435-1HG promotes cancer growth in clear cell renal cell carcinoma

BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in cancer development, yet their roles in renal carcinoma remain unclear. OBJECTIVE: We performed this study in order to investigate the expression and roles of lncRNAs in renal cell carcinoma. METHODS: In this study, we investigated the expression of lncRNAs in renal cell carcinoma through microarray analysis. Quantitative real-time PCR was performed to measure the expression of lncRNAs. Gain- or loss-of-function experiments were performed to investigate the roles of lncRNAs in cell proliferation and apoptosis. RNA pull-down and western blotting were performed to explore the underlying mechanism. RESULTS: The microarray analysis identified an upregulated lncRNA MIR4435-1HG in renal carcinoma. The expression level of MIR4435-1HG was correlated with TNM stage, tumor size, and Fuhrman grade. High expression of MIR4435-1HG indicated poor prognosis. MIR4435-1HG knockdown inhibited cell proliferation, and suppressed the migrating and invasive capacity of renal carcinoma cells. RNA pull-down followed by mass spectrometry revealed an interaction between MIR4435-1HG and pyruvate carboxylase, which was later corroborated by western blotting. CONCLUSIONS: MIR4435-1HG plays a critical role in the oncogenesis of renal cell carcinoma and may serve as a potential biomarker for renal cell carcinoma.

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Renal carcinoma related factor is up-regulated in high Fuhrman grade renal cell carcinoma tissues and affects prognosis of patients

Academic Journal of Second Military Medical University ◽

10.3724/sp.j.1008.2014.00566 ◽

2014 ◽

Vol 35 (5) ◽

pp. 566

Author(s):

Shang-qing SONG ◽

Zhen-jie WU ◽

Cheng WANG ◽

Bing LIU ◽

Lin-hui WANG

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Renal Carcinoma ◽

Related Factor ◽

Fuhrman Grade

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Interleukin-33 Predicts Poor Prognosis and Promotes Renal Cell Carcinoma Cell Growth Through its Receptor ST2 and the JNK Signaling Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000489766 ◽

2018 ◽

Vol 47 (1) ◽

pp. 191-200 ◽

Cited By ~ 10

Author(s):

Chang-wen Wu ◽

Yi-guo Wu ◽

Cheng Cheng ◽

Zheng-dong Hong ◽

Zi-min Shi ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Flow Cytometry ◽

Cell Proliferation ◽

Cell Growth ◽

Cell Carcinoma ◽

Western Blotting ◽

Renal Cell ◽

Jnk Signaling

Background/Aims: Renal cell carcinoma (RCC) is currently the ninth most common cancer in men. Interleukin (IL)-33 expression has previously been associated with a number of cancers; however, its biological role in RCC is poorly understood. In this study, we sought to elucidate the role of IL-33 in RCC. Methods: Serum IL-33 levels were measured by ELISA. IL-33 expression in clinical RCC samples was examined by immunocytochemistry. The proliferation and apoptosis rate of RCC were determined by CCK8 and flow cytometry. Mcl1 and Bcl-2 expression were measured by quantitative real-time PCR and western blotting. JNK expression were measured by western blotting and flow cytometry. The in vivo role of IL-33 in RCC tumorigenesis was examined by animal models. Results: We found that increased expression of IL-33 in RCC was associated with tumor-lymph node-metastasis (TNM) stage and inversely correlated with prognosis. IL-33 enhances RCC cell growth in vivo and stimulates RCC cell proliferation and prevents chemotherapy-induced tumor apoptosis in vitro. Furthermore, we demonstrated that IL-33 promotes RCC cell proliferation and chemotherapy resistance via its receptor ST2 and the JNK signaling activation in tumor cells. Conclusion: Our findings suggest that targeting IL-33/ST2 and JNK signaling may have potential value in the treatment of RCC.

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Plasma exosome microRNA-155 expression in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors: A potential biomarker of response to systemic therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4570 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4570-4570

Author(s):

Maryam Soleimani ◽

Marisa Thi ◽

Neetu Saxena ◽

Bernhard J. Eigl ◽

Daniel Joseph Khalaf ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Healthy Volunteers ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Immune Checkpoint ◽

Renal Cell ◽

Unmet Need ◽

First Line ◽

Fuhrman Grade ◽

Potential Biomarker

4570 Background: The search for a reliable predictive biomarker of response to immune checkpoint-based therapy (ICBT) remains a critically unmet need in the management of metastatic renal cell carcinoma (mRCC). We sought to evaluate the biomarker potential of plasma exosome microRNAs (miRNAs) implicated in RCC and in augmentation of the tumour microenvironment (TME) for such a role. Methods: Eleven miRNAs that are over-expressed in RCC and/or immune-associated were evaluated in 40 patients with mRCC (prior to initiating ICBT) and in 30 healthy volunteers. Exosomes were extracted from 500 uL of plasma and were used for miRNAs extraction. MiRNAs expression was evaluated by RT-PCR. Cycle threshold values were normalized to miR-30-3b, and the relative quantity of the expression (RQ) was compared to those of healthy volunteers and calculated using the 2ΔΔCt method. Mann-Whitney U test was used to evaluate the expression of miRNAs between mRCC pts and healthy volunteers according to best response to first line ICBT between responders (n = 27) v non-responders (n = 13). The cut-off value of significant expression was established by Youden’s index. Responders were defined as those patients experiencing complete response, partial response or stable disease and non-responders were those who experienced progressive disease. Results: The most common first line ICBT was nivolumab + ipilimumab (n = 32), followed by pembrolizumab + axitinib (n = 5), and avelumab + axitinib (n = 3). A significantly higher expression of miRNA-1233 (median 1.85 v 0.81 p = 0.008) and miRNA-155 [miR-155] (3.69 v 0.21 p = 0.006) were found in patients compared to healthy volunteers. Higher miR-155 expression was associated with higher Fuhrman grade (p = 0.002). There was no association with other clinical prognostic factors. MiR-155 was expressed at a significantly lower level in responders than in non-responders (median 0.61 v 35.29, p = 0.042). Response rate amongst patients with low and high expression of miR-155 (RQ ≤ 2.5) was statistically different (p = 0.042) and 84.2% of the pts with low miR-155 expression responded to the treatment. Conclusions: Lower expression of miR-155 was associated with response to ICBT in patients with mRCC. Functionally, miR-155 is involved in regulation and modulation of the TME. These results underscore the need for further work in this area to elucidate the role of this and other miRNAs as biomarkers of response in mRCC.

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Identification of Long Noncoding RNA APOC1P1 as an Oncogene in Clear Cell Renal Cell Carcinoma

Disease Markers ◽

10.1155/2019/2814058 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8

Author(s):

Chong Sun ◽

Zhonghan Zhou ◽

Haoqing Shi ◽

Fangzhou Li ◽

Guiming Zhang

Keyword(s):

Renal Cell Carcinoma ◽

Cell Proliferation ◽

Cell Carcinoma ◽

Long Noncoding Rna ◽

Renal Cell ◽

Noncoding Rna ◽

Migration And Invasion ◽

Normal Kidney ◽

Fuhrman Grade ◽

Kaplan Meier

Renal cell carcinoma (RCC) is one of the most common genitourinary cancers worldwide. Previous evidence shows that long noncoding RNA (LncRNA) APOC1P1 plays an important role in cancer development. However, the role of LncRNA APOC1P1 in ccRCC remains to be explored. LncRNA APOC1P1 expression in 283 ccRCC tissues and 30 normal kidney tissues was detected by quantitative real-time PCR, and its prognostic association with ccRCC was assessed by the Kaplan-Meier method and Cox proportional hazard model. Cell proliferation, apoptosis, migration, and invasion were determined in RCC cells with downregulation of LncRNA APOC1P1 expression. LncRNA APOC1P1 expression was increased in ccRCC tissues compared with normal kidney tissues (P<0.001). Its expression was higher in the Fuhrman grade III and IV group than in the Fuhrman grade I and II group (P<0.05) and significantly upregulated in the advanced stage group (P<0.05). Kaplan-Meier analyses revealed that elevated LncRNA APOC1P1 expression was significantly associated with poor overall survival (P<0.05) but may not be an independent prognostic factor. Knockdown of LncRNA APOC1P1 inhibited cell proliferation, induced apoptosis, and arrested cells at the G1/S phase (P<0.05). Silencing of LncRNA APOC1P1 also led to decreased cell migration and invasion (P<0.05). LncRNA APOC1P1 acts as an oncogene, plays an important role in ccRCC development, and can be considered a prognostic biomarker and therapeutic target in ccRCC patients.

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Inhibition of BRD4 Suppresses Cell Proliferation and Induces Apoptosis in Renal Cell Carcinoma

Cellular Physiology and Biochemistry ◽

10.1159/000472407 ◽

2017 ◽

Vol 41 (5) ◽

pp. 1947-1956 ◽

Cited By ~ 24

Author(s):

Xinchao Wu ◽

Dong Liu ◽

Xuemei Gao ◽

Fei Xie ◽

Dan Tao ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Proliferation ◽

Cell Carcinoma ◽

Renal Cell ◽

Molecular Mechanisms ◽

Critical Role ◽

Tumor Stage ◽

Promising Target

Background/Aims: Renal cell carcinoma (RCC) remains an intractable genitourinary malignancy. Resistance to chemotherapy or targeted therapies in RCC is presumably due to the complicated underlying molecular mechanisms and insufficient understanding. The aim of this research was to assess the expression and role of bromodomain-4 protein (BRD4) in RCC and evaluate the effects of BRD4 inhibitor JQ1 for RCC treatment. Methods: BRD4 expressionlevels were assessed by qRT-PCR and western blot in RCC tissues and cells. The effects of BRD4 knockdown or JQ1 on RCC cells were assessed by MTT assay and flow cytometry. The effects of in vivo treatment were evaluated through xenograft experiments. Results: BRD4 is significantly overexpressed in RCC, and is related to tumor stage and lymph node metastasis. Inhibition of BRD4 suppressed RCC cell proliferation, induced cell apoptosis in vitro and repressed tumor growth in vivo. Inhibition of BRD4 decreased BCL2 and C-MYC expression while increased BAX and cleaved caspase3 expression, and strikingly diminished the recruitment of BRD4 to BCL2 promoter. Conclusions: Our research reveals that BRD4 probably play a critical role in RCC progression, and is a new promising target for pharmacological treatment directed against this intractable disease.

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TRIM44 promotes cell proliferation and migration by inhibiting FRK in renal cell carcinoma

10.31234/osf.io/cm9wj ◽

2020 ◽

Author(s):

Lungwani Muungo

Keyword(s):

Renal Cell Carcinoma ◽

Cell Proliferation ◽

Cell Carcinoma ◽

Renal Cell ◽

Lymphatic Invasion ◽

Cancer Specific Survival ◽

Candidate Target ◽

Candidate Target Gene ◽

And Migration

TRIM44 has oncogenic roles in various cancers. However, TRIM44 expression andits function in renal cell carcinoma (RCC) are still unknown. Here in this study, weinvestigated the clinical significance of TRIM44 and its biological function in RCC.TRIM44 overexpression was significantly associated with clinical M stage, histologictype (clear cell) and presence of lymphatic invasion (P = .047, P = .005, and P = .028,respectively). Moreover, TRIM44 overexpression was significantly associated withpoor prognosis in terms of cancer-specific survival (P = .019). Gain-of-function andloss-of-function studies using TRIM44 and siTRIM44 transfection showed thatTRIM44 promotes cell proliferation and cell migration in two RCC cell lines, Caki1and 769P. To further investigate the role of TRIM44 in RCC, we performed integratedmicroarray analysis in Caki1 and 769P cells and explored the data in the Oncominedatabase. Interestingly, FRK was identified as a promising candidate target gene ofTRIM44, which was downregulated in RCC compared with normal renal tissues. Wefound that cell proliferation was inhibited by TRIM44 knockdown and then recoveredby siFRK treatment. Taken together, the present study revealed the associationbetween high expression of TRIM44 and poor prognosis in

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Nuclear and cytosolic pS727-STAT3 levels correlate with overall survival of patients affected by clear cell renal cell carcinoma (ccRCC)

Scientific Reports ◽

10.1038/s41598-021-86218-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jazmine Arévalo ◽

David Lorente ◽

Enrique Trilla ◽

María Teresa Salcedo ◽

Juan Morote ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Independent Manner ◽

Fuhrman Grade ◽

Transcription 3 ◽

Aggressive Subtype

AbstractClear cell renal cell carcinoma (ccRCC) is the most frequent and aggressive subtype of renal carcinoma. So far, the basis of its oncogenesis remains unclear resulting in a deficiency of usable and reliable biomarkers for its clinical management. Previously, we showed that nuclear expression of the signal transducer and activator of transcription 3 (STAT3), phosphorylated at its serine 727 (pS727), was inversely proportional to the overall survival of ccRCC patients. Therefore, in the present study, we validated the value of pS727-STAT3 as a clinically relevant biomarker in ccRCC. This work is a retrospective study on 82 ccRCC patients treated with nephrectomy and followed-up for 10 years. Immunohistochemical expression of pS727-STAT3 was analyzed on a tissue microarray and nuclear and cytosolic levels were correlated with clinical outcome of patients. Our results showed that pS727-STAT3 levels, whether in the nucleus (p = 0.002; 95% CI 1.004–1.026) or the cytosol (p = 0.040; 95% CI 1.003–1.042), significantly correlate with patients’ survival in an independent-manner of clinicopathological features (Fuhrman grade, risk group, and tumor size). Moreover, we report that patients with high pS727-STAT3 levels who undergone adjuvant therapy exhibited a significant stabilization of the disease (~ 20 months), indicating that pS727-STAT3 can pinpoint a subset of patients susceptible to respond well to treatment. In summary, we demonstrated that high pS727-STAT3 levels (regardless of their cellular location) correlate with low overall survival of ccRCC patients, and we suggested the use of pS727-STAT3 as a prognostic biomarker to select patients for adjuvant treatment to increase their survival.

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CMTM6 expression as a potential biomarker for immunotherapy in metastatic renal cell carcinoma

BJU International ◽

10.1111/bju.15341 ◽

2021 ◽

Author(s):

Gennadi Tulchiner ◽

Andrea Brunner ◽

Manuela Schmidinger ◽

Nina Staudacher ◽

Jacob J. Orme ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Potential Biomarker

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Development and characterization of a novel mAb against bilitranslocase - a new biomarker of renal carcinoma

Radiology and Oncology ◽

10.2478/raon-2013-0026 ◽

2013 ◽

Vol 47 (2) ◽

pp. 128-137 ◽

Cited By ~ 8

Author(s):

Sendi Montanic ◽

Michela Terdoslavich ◽

Uros Rajcevic ◽

Luigina De Leo ◽

Serena Department of Medical Sciences, Uni ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Monoclonal Antibodies ◽

Cell Carcinoma ◽

Renal Cell ◽

Renal Carcinoma ◽

Vascular Endothelial Cells ◽

Polyclonal Antibodies ◽

Functional Characterization ◽

Immunological Approach

Background. Bilitranslocase (TC 2.A.65.1.1) is a bilirubin-specific membrane transporter, found on absorptive (stomach and intestine) and excretory (kidney and liver) epithelia and in vascular endothelium. Polyclonal antibodies have been raised in rabbits in the past, using a synthetic peptide corresponding to AA65-77 of rat liver bilitranslocase, as an antigen. Affinity-purified antibodies from immune sera have been found to inhibit various membrane transport functions, including the bilirubin uptake into human hepatocytes and the uptake of some flavonoids into human vascular endothelial cells. It was described by means of immunohistochemistry using polyclonal antibodies that bilitranslocase expression is severely down-regulated in clear cell renal carcinoma. The aim of our work was development and characterization of high-affinity, specific mAbs against bilitranslocase, which can be used as a potential diagnostic tool in renal cell carcinoma as well as in a wide variety of biological assays on different human tissues. Materials and methods. Mice were immunized with a multi-antigen peptide corresponding to segment 65-75 of predicted primary structure of the bilitranslocase protein. By a sequence of cloning, immune- and functional tests, we aimed at obtaining a specific monoclonal antibody which recognizes a 37 kDa membrane protein, and influences the transport activity of bilitranslocase. Results. On the basis of previous results, specific IgM monoclonal antibodies were produced in BALB/c mice, in order to further improve and extend the immunological approach to the study of bilitranslocase in renal cancer cells as well as to develop its potential diagnostics use. Conclusions. In this article we show an immunological approach, based on newly developed monoclonal antibodies, to a detailed biochemical and functional characterization of a protein whose gene and protein structure is still unknown. We were able to demonstrate our novel mAb as a tumor marker candidate of renal cell carcinoma, which may prove useful in the diagnostic procedures.

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