IgG is involved in the migration and invasion of clear cell renal cell carcinoma

OBJECTIVE:To investigate if IgG can be expressed in clear cell renal cell carcinoma (cRCC) , and the expression of IgG is involved in the cancer progression. If IgG expression can serve as a potential target in cancer therapies and be used for judging the prognosis.MATERIALS AND METHODS:By immunohistochemistry, we detected IgG in cRCC tissues(75 cRCC tissues and75 adjacent normal kidney tissues). Immunofluorescence and Western blot was used to detect the IgG in cRCC cell lines (786-0, ACHN and CAKI-I). By RT-PCR, the functional transcript of IgG heavy chain was detected. Knockdown of IgG was to analyze the proliferation, migration and invasion ability by CCK8, Transwell and Matrigel and apoptosis in cRCC cell lines.RESULTS:By immunohistochemistry, we found strong staining of IgG in 66 cases of 75 cRCC tissues and 63 cases of 75 adjacent normal kidney tissues. Immunofluorescence and Western blot was found IgG in cRCC cell lines. Knock-down IgG in cRCC cell lines resulted in significant inhibition of cell proliferation, migration and invasion, and the induction of apoptosis of the 786-0 cells. The immunohistochemistry analysis showed that high IgG expression significantly correlated with the poor differentiation and advanced stage of cRCC.CONCLUSION:IgG was over expressed in cRCC and was involved in the proliferation, migration and invasion of cancer cells. IgG expression may serve as a potential target in cancer therapies and could be used for judging the prognosis.

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CircUBAP2 Inhibits Proliferation and Metastasis of Clear Cell Renal Cell Carcinoma via Targeting miR-148a-3p/FOXK2 Pathway

Cell Transplantation ◽

10.1177/0963689720925751 ◽

2020 ◽

Vol 29 ◽

pp. 096368972092575

Author(s):

Jiping Sun ◽

Aiping Yin ◽

Wenjing Zhang ◽

Jia Lv ◽

Yu Liang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Cell Lines ◽

Renal Cell ◽

Clear Cell ◽

Underlying Mechanism ◽

Migration And Invasion ◽

Inhibitory Effects ◽

Cell Renal Cell Carcinoma ◽

Ribonucleic Acids

Clear cell renal cell carcinoma (ccRCC) is the prominent histological subtype of renal cell carcinoma (RCC) with high incidence of local recurrence and distant metastasis. It has been documented that circular ribonucleic acids (circRNAs) play crucial roles in the development of cancers; however, study on exploring the role of circRNAs in ccRCC still remains limited. In the present study, we aimed to evaluate the biological function of a novel circRNA UBAP2 (circUBAP2) in ccRCC and the underlying mechanism. Our results showed that circUBAP2 expression was significantly down-regulated in ccRCC tissues and cell lines. Overexpression of circUBAP2 significantly inhibited the proliferation, migration, and invasion of ccRCC cells. MiR-148a-3p was a target miRNA of circUBAP2 in ccRCC cells, and its expression levels in ccRCC tissues and cell lines were negatively correlated with circUBAP2 levels. Moreover, miR-148a-3p reversed the inhibitory effects of circUBAP2 on cell proliferation, migration, and invasion in ccRCC cells. Additionally, forkhead box K2 (FOXK2) was found to be a target gene of miR-148a-3p and regulated by miR-148a-3p in ccRCC cells. Furthermore, knockdown of FOXK2 reversed the inhibitory effects of miR-148a-3p inhibitor on ccRCC cells. In conclusion, these findings indicated that circUBAP2 functioned as a novel tumor suppressor in ccRCC through regulating the miR-148a-3p/FOXK2 axis. Therefore, circUBAP2 might serve as a potential therapeutic target for the treatment of ccRCC.

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Upregulation of MIAT Regulates LOXL2 Expression by Competitively Binding MiR-29c in Clear Cell Renal Cell Carcinoma

Cellular Physiology and Biochemistry ◽

10.1159/000491974 ◽

2018 ◽

Vol 48 (3) ◽

pp. 1075-1087 ◽

Cited By ~ 30

Author(s):

Yan Qu ◽

Haibing Xiao ◽

Wen Xiao ◽

Zhiyong Xiong ◽

Wenjun Hu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Proliferation ◽

Western Blot ◽

Cell Carcinoma ◽

Cell Lines ◽

Renal Cell ◽

Molecular Mechanisms ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Proliferation And Metastasis

Background/Aims: MIAT is a long noncoding RNA (lncRNA) involved in cell proliferation and the development of tumor. However, the exact effects and molecular mechanisms of MIAT in clear cell renal cell carcinoma (ccRCC) progression are still unknown. Methods: We screened the lncRNAs’ profile of ccRCC in The Cancer Genome Atlas database, and then examined the expression levels of lncRNA MIAT in 45 paired ccRCC tissue specimens and in cell lines by q-RT-PCR. MTS, colony formation, EdU, and Transwell assays were performed to examine the effect of MIAT on proliferation and metastasis of ccRCC. Western blot and luciferase assays were performed to determine whether MIAT can regulate Loxl2 expression by competitively binding miR-29c in ccRCC. Results: MIAT was up-regulated in ccRCC tissues and cell lines. High MIAT expression correlated with worse clinicopathological features and shorter survival rate. Functional assays showed that knockdown of MIAT inhibited renal cancer cell proliferation and metastasis in vitro and in vivo. Luciferase and western blot assays further confirmed that miR-29c binds with MIAT. Additionally, the correlation of miR-29c with MIAT and Loxl2 was further verified in patients' samples. Conclusion: Our data indicated that MIAT might be an oncogenic lncRNA that promoted proliferation and metastasis of ccRCC, and could be a potential therapeutic target in human ccRCC.

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hZIP1 Inhibits Progression of Clear Cell Renal Cell Carcinoma by Suppressing NF-kB/HIF-1α Pathway

Frontiers in Oncology ◽

10.3389/fonc.2021.759818 ◽

2021 ◽

Vol 11 ◽

Author(s):

Bo Zhan ◽

Xiao Dong ◽

Yulin Yuan ◽

Zheng Gong ◽

Bohan Li

Keyword(s):

Renal Cell Carcinoma ◽

Western Blot ◽

Cell Carcinoma ◽

Cell Lines ◽

Nude Mice ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Protein Levels ◽

Ccrcc Cell

PurposeAccumulating literature has suggested that hZIP1 and HIF-1α play vital roles in the tumor process of clear cell renal cell carcinoma (ccRCC). However, the functional roles of hZIP1 and HIF-1α in ccRCC remain largely unknown.MethodsHIF-1α protein level was evaluated by a western blot in ccRCC tissues and cell lines. ccRCC cell lines were transfected with HIF-1α-siRNA to downregulate the expression level of HIF-1α. Then the proliferative, migratory and invasive abilities of ccRCC cells in vitro were detected by real-time cell analysis (RTCA) assay, wound healing assay and transwell assay, respectively. The role of HIF-1α in vivo was explored by tumor implantation in nude mice. Then the effect on glycolysis‐related proteins was performed by western blot after hZIP1 knockdown (overexpression) or HIF-1α knockdown. The effect on NF‐kB pathway was detected after hZIP1 overexpression.ResultsHIF-1α was markedly downregulated in ccRCC tissues compared with normal areas. But HIF-1α presented almost no expression in HK-2 and ACHN cells. Immunofluorescence indicated HIF-1α and PDK1 expression in both the cytoplasm and nucleus in ccRCC cells. Downregulation of HIF-1α suppressed ccRCC cell proliferation, migration, and invasion and resulted in smaller implanted tumors in nude mice. Furthermore, hZIP1 knockdown elevated HIF-1α protein levels and PDK1 protein levels in ccRCC cells. Interestingly, a sharp downregulated expression of HIF-1α was observed after hZIP1 overexpression in OSRC-2 and 786-O cells, which resulted from a downtrend of NF-kB1 moving into the cell nucleus.ConclusionOur work has vital implications that hZIP1 suppresses ccRCC progression by inhibiting NF-kB/HIF-1α pathway.

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MiR-224-5p Targeting OCLN Promotes the Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma Cells

Urologia Internationalis ◽

10.1159/000515981 ◽

2021 ◽

pp. 1-10

Author(s):

Yifei Liu ◽

Honglin Nie ◽

Yubo Zhang ◽

Na Zhang ◽

Miaomiao Han ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Cell Lines ◽

Renal Cell ◽

Clear Cell ◽

Physiological Role ◽

Luciferase Assay ◽

Migration And Invasion ◽

Cell Renal Cell Carcinoma ◽

Ccrcc Cell

A number of studies reported that miR-224-5p is involved in a variety of cancer-related cellular processes, yet its physiological role in clear cell renal cell carcinoma (ccRCC) remains unclear. In order to clarify the function of miR-224-5p in ccRCC, real-time quantitative-PCR was conducted to compare the expression of miR-224-5p in human normal renal tubular epithelial cell lines and ccRCC cell lines first, and a strikingly upregulated expression was observed in ccRCC cell lines. Inhibition of miR-224-5p expression by microRNA inhibitors could inhibit the proliferation, migration, and invasion of ccRCC cells. Besides, it was validated by dual-luciferase assay in which miR-224-5p directly targeted OCLN gene. The expression of OCLN was downregulated in ccRCC cells, and overexpression of miR-224-5p could inhibit the mRNA and protein expression levels of OCLN. Overexpression of OCLN could reduce the proliferation, migration, and invasion of ccRCC cells, while overexpressed miR-224-5p could partially reverse that inhibitory effect. Therefore, the promotive effect of miR-224-5p on the proliferation, invasion, and migration of ccRCC cell lines was at least partly due to the inhibition of OCLN expression. These findings highlighted the important function of miR-224-5p, which was promoting cell proliferation, migration, and invasion by downregulating OCLN, in the pathogenesis of ccRCC, and provided a potential treatment strategy.

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Positive feedback regulation of lncRNA PVT1 and HIF2α contributes to clear cell renal cell carcinoma tumorigenesis and metastasis

Oncogene ◽

10.1038/s41388-021-01971-7 ◽

2021 ◽

Author(s):

Ming-xiao Zhang ◽

Li-zhen Zhang ◽

Liang-min Fu ◽

Hao-hua Yao ◽

Lei Tan ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Positive Feedback ◽

Renal Cell ◽

Clear Cell ◽

Biological Significance ◽

Specific Inhibitor ◽

Migration And Invasion ◽

Loss Of Function ◽

Cell Renal Cell Carcinoma

AbstractLong noncoding RNAs (lncRNAs) have been reported to exert important roles in tumors, including clear cell renal cell carcinoma (ccRCC). PVT1 is an important oncogenic lncRNA which has critical effects on onset and development of various cancers, however, the underlying mechanism of PVT1 functioning in ccRCC remains largely unknown. VHL deficiency-induced HIF2α accumulation is one of the major factors for ccRCC. Here, we identified the potential molecular mechanism of PVT1 in promoting ccRCC development by stabilizing HIF2α. PVT1 was significantly upregulated in ccRCC tissues and high PVT1 expression was associated with poor prognosis of ccRCC patients. Both gain-of-function and loss-of function experiments revealed that PVT1 enhanced ccRCC cells proliferation, migration, and invasion and induced tumor angiogenesis in vitro and in vivo. Mechanistically, PVT1 interacted with HIF2α protein and enhanced its stability by protecting it from ubiquitination-dependent degradation, thereby exerting its biological significance. Meanwhile, HIF2α bound to the enhancer of PVT1 to transactivate its expression. Furthermore, HIF2α specific inhibitor could repress PVT1 expression and its oncogenic functions. Therefore, our study demonstrates that the PVT1/ HIF2α positive feedback loop involves in tumorigenesis and progression of ccRCC, which may be exploited for anticancer therapy.

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