Human anti-CAIX antibodies mediate immune cell inhibition of renal cell carcinoma in vitro and in a humanized mouse model in vivo

Abstract Background There is increasing evidence that circular RNAs (circRNAs) have significant regulatory roles in cancer development and progression; however, the expression patterns and biological functions of circRNAs in renal cell carcinoma (RCC) remain largely elusive. Method Bioinformatics methods were applied to screen for circRNAs differentially expressed in RCC. Analysis of online circRNAs microarray datasets and our own patient cohort indicated that circSDHC (hsa_circ_0015004) had a potential oncogenic role in RCC. Subsequently, circSDHC expression was measured in RCC tissues and cell lines by qPCR assay, and the prognostic value of circSDHC evaluated. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of circSDHC on RCC proliferation and metastasis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between circSDHC, miR-127-3p and its target genes. Results Clinically, high circSDHC expression was correlated with advanced TNM stage and poor survival in patients with RCC. Further, circSDHC promoted tumor cell proliferation and invasion, both in vivo and in vitro. Analysis of the mechanism underlying the effects of circSDHC in RCC demonstrated that it binds competitively to miR-127-3p and prevents its suppression of a downstream gene, CDKN3, and the E2F1 pathway, thereby leading to RCC malignant progression. Furthermore, knockdown of circSDHC caused decreased CDKN3 expression and E2F1 pathway inhibition, which could be rescued by treatment with an miR-127-3p inhibitor. Conclusion Our data indicates, for the first time, an essential role for the circSDHC/miR-127-3p/CDKN3/E2F1 axis in RCC progression. Thus, circSDHC has potential to be a new therapeutic target in patients with RCC.

Download Full-text

Synergistic immunotherapeutic effects of Lycium barbarum polysaccharide and interferon-α2b on the murine Renca renal cell carcinoma cell line in vitro and in vivo

Molecular Medicine Reports ◽

10.3892/mmr.2015.4230 ◽

2015 ◽

Vol 12 (5) ◽

pp. 6727-6737 ◽

Cited By ~ 19

Author(s):

SHIYOU CHEN ◽

LUNAN LIANG ◽

YING WANG ◽

JIANHUN DIAO ◽

CHUNXIONG ZHAO ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Carcinoma Cell ◽

Lycium Barbarum ◽

Renal Cell Carcinoma Cell ◽

Lycium Barbarum Polysaccharide ◽

Interferon Α2b

Download Full-text

MicroRNA-373 promotes tumorigenesis of renal cell carcinoma in vitro and in vivo

Molecular Medicine Reports ◽

10.3892/mmr.2017.7443 ◽

2017 ◽

Vol 16 (5) ◽

pp. 7048-7055 ◽

Cited By ~ 5

Author(s):

Yanli Li ◽

Da Zhang ◽

Jiaxiang Wang

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell

Download Full-text

ATF3 Suppresses Growth and Metastasis of Clear Cell Renal Cell Carcinoma by Deactivating EGFR/AKT/GSK3β/β-Catenin Signaling Pathway

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.618987 ◽

2021 ◽

Vol 9 ◽

Author(s):

Shenglin Gao ◽

Lei Gao ◽

Simin Wang ◽

Xiaokai Shi ◽

Chuang Yue ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Mouse Model ◽

Cell Carcinoma ◽

Signaling Pathway ◽

Renal Cell ◽

Clear Cell ◽

Invasion Assay ◽

Cell Renal Cell Carcinoma ◽

Atf3 Expression

BackgroundClear cell renal cell carcinoma (ccRCC) is one of the most common malignant cancers in East Asia, with high incidence and mortality. Accumulating evidence has shown that ATF3 is associated with tumor progression.MethodsUsing qPCR, the expression of ATF3 was detected in 93 patients with ccRCC, including 24 paired normal and tumor tissues, which were used to further compare ATF3 expression through western blotting and immunohistochemistry. Lentivirus was used for the overexpression or knockdown of ATF3, and the consequent alteration in function was analyzed through CCK8 assay, colony formation assay, wound healing assay, invasion assay, and flow cytometry. The potential mechanism affected by ATF3 was analyzed through gene set enrichment analysis (GSEA) and verified using western blotting, invasion assay, or immunofluorescence staining. Furthermore, a xenograft mouse model was used to assess the function of ATF3 in vivo.ResultsATF3 expression was significantly decreased in ccRCC compared to that in adjacent normal tissues. Through gain- and loss-of-function experiments performed in an in vitro assay, we found that ATF3 could regulate ccRCC cell proliferation, cycle progression, migration, and invasion. In the in vivo study, the xenograft mouse model revealed that ATF3 overexpression can inhibit the growth of ccRCC. Moreover, the mechanism analysis showed that suppression of ATF3 could lead to an increase the expression of β-catenin and promote β-catenin transfer to the nucleus, and might be affected by EGFR/AKT/GSK3β signaling.ConclusionATF3 could be utilized as an independent protective factor to inhibit the progression of ccRCC. Potential treatment strategies for ccRCC include targeting the ATF3/EGFR/AKT/GSK3β/β−catenin signaling pathway.

Download Full-text

GV1001 Induces Apoptosis by Reducing Angiogenesis in Renal Cell Carcinoma Cells Both In Vitro and In Vivo

Urology ◽

10.1016/j.urology.2017.10.038 ◽

2018 ◽

Vol 113 ◽

pp. 129-137 ◽

Cited By ~ 4

Author(s):

Ga Eun Kim ◽

Ae Ryang Jung ◽

Mee Young Kim ◽

Joseph Bada Lee ◽

Ji Houn Im ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Carcinoma Cells

Download Full-text

Long Non-Coding RNA LINC02747 Promotes the Proliferation of Clear Cell Renal Cell Carcinoma by Inhibiting miR-608 and Activating TFE3

Frontiers in Oncology ◽

10.3389/fonc.2020.573789 ◽

2020 ◽

Vol 10 ◽

Author(s):

Xiang Ju ◽

Yangyang Sun ◽

Feng Zhang ◽

Xiaohui Wei ◽

Zhenguo Wang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Histological Grade ◽

Rapid Development ◽

The Cancer Genome Atlas ◽

Cell Renal Cell Carcinoma

With the rapid development of biotechnology, long noncoding RNAs (lncRNAs) have exhibited good application prospects in the treatment of cancer, and they may become new treatment targets for cancer. This study aimed to explore lncRNAs in clear cell renal cell carcinoma (ccRCC). Differentially expressed lncRNAs in 54 pairs of ccRCC tissues and para-carcinoma tissues were analyzed in The Cancer Genome Atlas (TCGA), and the most significant lncRNAs were selected and verified in ccRCC tissues. We found that lncRNA LINC02747 was highly expressed in ccRCC (P < 0.001) and was closely related to high TNM stage (P = 0.006) and histological grade (P = 0.004) and poor prognosis of patients (P < 0.001). In vivo and in vitro experiments confirmed that LINC02747 could promote the proliferation of ccRCC cells. We also found that LINC02747 regulated the proliferation of RCC cells by adsorbing miR-608. Subsequent mechanistic research showed that miR-608 is downregulated in ccRCC (P < 0.001), and overexpression of miR-608 inbibited the proliferation of RCC cells. Moreover, we found that TFE3 is a direct target gene of miR-608. MiR-608 regulated the proliferation of RCC cells by inhibiting TFE3. In conclusion, LINC02747 upregulates the expression of TFE3 by adsorbing miR-608, ultimately promoting the proliferation of ccRCC cells. The above findings indicate that LINC02747 acts as an oncogene in ccRCC and may be developed as a molecular marker for the diagnosis and prognosis of ccRCC. The LINC02747/miR-608/TFE3 pathway may become a new therapeutic target for ccRCC.

Download Full-text

Kinesin Motor Protein KIFC1 Is a Target Protein of miR-338-3p and Is Associated With Poor Prognosis and Progression of Renal Cell Carcinoma

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504018x15213115046567 ◽

2018 ◽

Vol 27 (1) ◽

pp. 125-137 ◽

Cited By ~ 11

Author(s):

Gang Li ◽

Tie Chong ◽

Jie Yang ◽

Hongliang Li ◽

Haiwen Chen

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Therapeutic Target ◽

Renal Cell ◽

Critical Role ◽

Survival Prognosis ◽

Inhibition Of Proliferation ◽

Invasion And Migration

KIFC1 (kinesin family member C1) plays a critical role in clustering of extra centrosomes in various cancer cells and thus could be considered as a promising therapeutic target. However, whether KIFC1 is involved in the procession of renal cell carcinoma (RCC) still remains unclear. In this study, we found that KIFC1 was upregulated in RCC tissues and is responsible for RCC tumorigenesis (p < 0.001). The high expression of KIFC1 correlates with aggressive clinicopathologic parameters. Kaplan‐Meier analysis suggested that KIFC1 was associated with poor survival prognosis in RCC. Silencing KIFC1 dramatically resulted in inhibition of proliferation, delayed the cell cycle at G2/M phase, and suppressed cell invasion and migration in vitro. The antiproliferative effect of KIFC1 silencing was also observed in xenografted tumors in vivo. miR-338-3p could directly bind to the 3′-untranslated region (3′-UTR) of KIFC1, and ectopic miR-338-3p expression mimicked the inhibitory functions of KIFC1 silencing on RCC cells through inactivation of the PI3K/AKT signaling pathway. Therefore, these results revealed that KIFC1 may be a novel biomarker and an effective therapeutic target for the treatment of RCC.

Download Full-text

Synergistic antitumor effect of ionomycin and cisplatin against renal cell carcinoma in vitro and in vivo

Urology ◽

10.1016/s0090-4295(00)00875-x ◽

2001 ◽

Vol 57 (1) ◽

pp. 188-192 ◽

Cited By ~ 1

Author(s):

Masayuki Okamoto ◽

Isao Hara ◽

Hideaki Miyake ◽

Shoji Hara ◽

Akinobu Gotoh ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Antitumor Effect ◽

Synergistic Antitumor Effect

Download Full-text

Bromodomain-Containing Protein 4 (BRD4) Inhibition Sensitizes Palomid 529-Induced Anti-Renal Cell Carcinoma Cell Activity in Vitro and in Vivo

Cellular Physiology and Biochemistry ◽

10.1159/000494185 ◽

2018 ◽

Vol 50 (2) ◽

pp. 640-653 ◽

Cited By ~ 2

Author(s):

Zhao-yu Xing ◽

Yin Wang ◽

Long Cheng ◽

Jie Chen ◽

Xiao-zhou He ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Growth ◽

Cell Carcinoma ◽

Cell Apoptosis ◽

Renal Cell ◽

Elisa Assay ◽

Dual Inhibitor ◽

Brd4 Inhibition

Background/Aims: Mammalian target of rapamycin (mTOR) is a valuable treatment target of renal cell carcinoma (RCC). Palomid 529 is a novel mTORC1/2 dual inhibitor. Methods: RCC cells were treated with different concentrations of Palomid 529. Cell survival was tested by MTT assay and clonogenicity assay. Cell proliferation was tested by BrdU ELISA assay. Cell apoptosis was tested by the Hoechst-33342 nuclei staining assay and Histone DNA ELISA assay. mTOR signaling was tested by Western blotting assay and co-immunoprecipitation (IP) assay. The SCID mouse 786-O xenograft model was established to test RCC cell growth in vivo. Results: Palomid 529 exerted cytotoxic, anti-proliferative and pro-apoptotic activities in 786-O RCC cells. Palomid 529 disassembled mTORC1/2, causing de-phosphorylation of mTORC1/2 substrates. Bromodomain-containing protein 4 (BRD4) is a primary resistant factor of Palomid 529. Palomid 529-induced 786-O cell apoptosis was sensitized by BRD4 inhibitors or BRD4 silencing, but inhibited with BRD4 over-expression. Palomid 529-induced cytotoxicity in the primary human RCC cells was negatively correlated with BRD4 expression level. In vivo, Palomid 529 i.p. administration inhibited 786-O xenograft tumor growth in SCID mice. Its anti-tumor activity was further sensitized by co-administration of the BRD4 inhibitor JQ1. Cconclusion: Palomid 529 inhibits RCC cell growth in vitro and in vivo. BRD4 inhibition could further sensitize Palomid 529 against RCC cells.

Download Full-text