scholarly journals SNHG16 promotes cell proliferation and inhibits cell apoptosis via regulation of the miR-1303p/STARD9 axis in renal cell carcinoma

2021 ◽  
Author(s):  
Tao Cheng ◽  
Weibing Shuang ◽  
Dawen Ye ◽  
Wenzhi Zhang ◽  
Zhao Yang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Cell Apoptosis ◽  
Renal Cell ◽  
Target Gene ◽  
Quantitative Polymerase Chain Reaction ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
High Morbidity

AbstractBackgroundRenal cell carcinoma (RCC) is a fatal malignant tumor with high morbidity. Numerous medical studies have suggested that long noncoding RNAs (lncRNAs) exert their biological function on various cancerous progresses. Herein, functions of lncRNA SNHG16 in RCC cells and the mechanism medicated by SNHG16 were investigated.MethodsThe expression levels of SNHG16 and its downstream genes in RCC cells and tissues were examined utilizing reverse transcription quantitative polymerase chain reaction analyses. Cell counting kit-8 and 5-Ethynyl-2’-deoxyuridine assays were carried out to evaluate the proliferation of RCC cells, and flow cytometry analyses were employed to determine the apoptosis of RCC cells. Western blot analysis was applied to examine protein levels associated with cell proliferation and apoptosis. The combination between SNHG16 and miRNA as well as miRNA and its target gene were explored by luciferase reporter, RNA pull down, and RNA immunoprecipitation assays.ResultsThe significant upregulation of SNHG16 was observed in RCC tissues and cells. SNHG16 downregulation inhibited the proliferation and promoted the apoptosis of RCC cells. In addition, SNHG16 served as a competing endogenous RNA for miR-1301-3p, and STARD9 was a target gene of miR-1301-3p in RCC cells. SNHG16 upregulated STARD9 expression by binding with miR-1301-3p in RCC cells. Rescue assays validated that SNHG16 promoted RCC cell promotion and induced RCC cell apoptosis by upregulating STARD9 expression.ConclusionsSNHG16 promotes RCC cell proliferation and suppresses RCC cell apoptosis via interaction with miR-1301-3p to upregulate STARD9 expression in RCC cells.

scholarly journals Long noncoding RNA SNHG4 promotes renal cell carcinoma tumorigenesis and invasion by acting as ceRNA to sponge miR-204-5p and upregulate RUNX2

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jie Wu ◽  
Tingting Liu ◽  
Lulu Sun ◽  
Shaojin Zhang ◽  
Gang Dong
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Mouse Models ◽  
Cell Lines ◽  
Renal Cell ◽  
Cell Counting ◽  
Tissue Samples ◽  
Qrt Pcr

Abstract Background Long noncoding RNAs (lncRNAs) are involved in the tumorigenesis and progression of human cancers, including renal cell carcinoma (RCC). Small nucleolar RNA host gene 4 (SNHG4) is reported to play an essential role in tumor growth and progression. However, the molecular mechanisms and function of SNHG4 in RCC remain undocumented. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine expression levels of SNHG4 in RCC tissue samples and cell lines. Cell counting kit-8, western blotting, activities of caspase-3, -8, and -9, wound-healing, and transwell invasion assays were performed to explore cell proliferation, apoptosis, migration, and invasion. The interaction among SNHG4, miR-204-5p, and RUNX2 was verified by bioinformatic analysis, a luciferase gene report, qRT-PCR, western blot analysis, and RNA immunoprecipitation assays. Xenograft mouse models were carried out to examine the role of SNHG4 in RCC in vivo. Results SNHG4 was highly expressed in RCC tissue samples and cell lines, and its upregulation was significantly involved in node involvement, distant metastasis, and reduced overall and relapse-free survival of patients with RCC. SNHG4 acted as an oncogenic lncRNA with promoted RCC cell proliferation, migration, invasion, and inhibited apoptosis. SNHG4 boosted tumor growth in xenograft mouse models. Mechanistically, SNHG4 functioned as a competing endogenous RNA (ceRNA) for sponging miR-204-5p, leading to the upregulation of its target RUNX2 to promote RCC cell proliferation and invasion. Conclusion SNHG4 and miR-204-5p might be indicated in RCC progression via RUNX2, suggesting the potential use of SNHG4/miR-204-5p/RUNX2 axis in RCC treatment.

scholarly journals Mir-144-3p Promotes Cell Proliferation, Metastasis, Sunitinib Resistance in Clear Cell Renal Cell Carcinoma by Downregulating ARID1A

2017 ◽  
Vol 43 (6) ◽  
pp. 2420-2433 ◽  
Author(s):  
Wen Xiao ◽  
Ning Lou ◽  
Hailong Ruan ◽  
Lin Bao ◽  
Zhiyong Xiong ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Cell Renal Cell Carcinoma

Background/Aims: We previously performed microRNA (miRNA) microarray to identify effective indicators of clear cell renal cell carcinoma (ccRCC) tissue samples and preoperative/postoperative plasma in which we identified miR-144-3p as an oncomiRNA. However, the molecular mechanism of miR-144-3p remains unclear. This study aims to explore the roles of miR-144-3p in the invasion, migration and Sunitinib-resistance in ccRCC and to elucidate the underlying mechanisms. Methods: Gain and loss of function approaches were used to investigate the cell proliferation, cycle distribution, clonogenicity, migration, invasion, chemosensitivity of miR-144-3p in vitro. The xenograft model was used to assess the effects of miR-144-3p overexpression on tumorigenesis. Bioinformatics analysis and dual-luciferase reporter assay were used to indentify AT-rich interactive domain 1A (ARID1A) as a direct target gene of miR-144-3p. Quantitative RT-PCR, Western blotting, and immunohistochemical (IHC) staining were used to explore ARID1A expression level of the mRNA and protein. Results: We found that miR-144-3p overexpression enhanced cell proliferation, clonogenicity, migration, invasion, and chemoresistance in ccRCC cells. Notably, the oncotumor activities of miR-144-3p were mediated by repressing the expression of ARID1A. The downregulation of ARIDIA could promote the function of miR-144-3p in cell proliferation, metastasis and chemoresistance. Consistently, ARID1A mRNA and protein levels were decreased in ccRCC and in nude mice, and they negatively correlated with miR-144-3p. Conclusion: Higher miR-144-3p may enhance malignancy and resistance to Sunitinib in ccRCC by targeting ARID1A, the observations may uncover novel strategies of ccRCC treatment.

scholarly journals LncRNA TP73-AS1 Promotes Cell Proliferation and Inhibits Cell Apoptosis in Clear Cell Renal Cell Carcinoma Through Repressing KISS1 Expression and Inactivation of PI3K/Akt/mTOR Signaling Pathway

2018 ◽  
Vol 48 (1) ◽  
pp. 371-384 ◽  
Author(s):  
Guanghua Liu ◽  
Xin Zhao ◽  
Jingmin Zhou ◽  
Xiangming Cheng ◽  
Zixing Ye ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Renal Cell ◽  
Clear Cell ◽  
Mtor Signaling ◽  
Metastasis Suppressor ◽  
Mtor Signaling Pathway

Background/Aims: Emerging evidence suggests that long non-coding RNAs (lncRNAs) play a vital regulatory role in the pathogenesis and progression of renal cell carcinoma (RCC). We aim to determine lncRNA profiles in clear cell RCC (ccRCC) and investigate key lncRNAs involved in ccRCC tumorigenesis and progression. Methods: RNA sequencing technique and qPCR were used to determine the candidate lncRNAs in ccRCC tissues. The correlations between lncRNA P73 antisense RNA 1T (TP73-AS1) levels and survival outcomes were analyzed to elucidate its clinical significance. The underlying mechanisms of TP73-AS1 in ccRCC were analyzed through in vitro functional assays. Results: We found TP73-AS1 was upregulated in 40 ccRCC tissues compared with adjacent normal renal tissues and increased TP73-AS1 was correlated to aggressive clinicopathologic features and unfavorable prognosis. Knockdown of TP73-AS1 suppressed cell proliferation, invasion and induced cell apoptosis. We also identified KISS-1 metastasis-suppressor (KISS1) was significantly upregulated in TP73-AS1 knockdown cells. Further, we revealed that TP73-AS1 suppressed KISS1 expression through the interaction with Enhancer of zeste homolog 2 (EZH2) and the specific binding to KISS1 gene promoter region. Knockdown of KISS1 partly reversed TP73-AS1 knockdown-induced inhibition of cell proliferation and promotion of apoptosis. We further determined that TP73-AS1 knockdown activated PI3K/Akt/mTOR signaling pathway, while overexpression of TP73-AS1 induced inhibition of PI3K/Akt/mTOR pathway and these effects could be partly abolished by overexpression of KISS1. Conclusion: In conclusion, we identified that TP73-AS1 as an oncogenic lncRNA in the development of ccRCC and a potential target for human renal carcinoma treatment.

scholarly journals LncRNA UCA1 promotes renal cell carcinoma proliferation through epigenetically repressing p21 expression and negatively regulating miR-495

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770163 ◽  
Author(s):  
Yun Lu ◽  
Wei-Gang Liu ◽  
Jia-Hui Lu ◽  
Zhi Jun Liu ◽  
Hai-Bin Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Urothelial Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Phase Cell ◽  
Luciferase Reporter ◽  
Advanced Tumor Stage ◽  
Advanced Tumor ◽  
Enhancer Of Zeste

Long non-coding RNAs have recently emerged as important regulators in the pathogenesis and progression of cancers. The long non-coding RNA urothelial carcinoma–associated 1 is reportedly upregulated and functions as an oncogene in some tumors. However, the role of urothelial carcinoma–associated 1 in renal cell carcinoma is not well elucidated so far. In this study, we found that urothelial carcinoma–associated 1 was overexpressed in renal cell carcinoma tissues compared with the adjacent normal tissues, and higher urothelial carcinoma–associated 1 expression levels were positively associated with advanced tumor stage and poor survival time in renal cell carcinoma patients. Further studies showed that knockdown of urothelial carcinoma–associated 1 suppressed renal cell carcinoma cell proliferation and S-phase cell number in vitro. Moreover, urothelial carcinoma–associated 1 was found to be associated with enhancer of zeste homolog 2, which suppressed p21 expression through histone methylation (H3K27me3) on p21 promoter. We also showed that knockdown of urothelial carcinoma–associated 1 increased the p21 protein expression through regulating enhancer of zeste homolog 2. In addition, bioinformatics analysis and dual-luciferase reporter assays confirmed that miR-495 was a target of urothelial carcinoma–associated 1 in renal cell carcinoma, and urothelial carcinoma–associated 1 promoted cell proliferation by negatively regulating miR-495. These findings illuminated that urothelial carcinoma–associated 1 promoted renal cell carcinoma progression through enhancer of zeste homolog 2 and interacted with miR-495. Overall, overexpression of urothelial carcinoma–associated 1 functions as an oncogene in renal cell carcinoma that may offer a novel therapeutic target for renal cell carcinoma patients.

scholarly journals Long noncoding RNA LINC00641 promotes renal cell carcinoma progression via sponging microRNA-340-5p

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jianping Zhang ◽  
Shengming Jin ◽  
Wenjun Xiao ◽  
Xuchao Zhu ◽  
Chengyou Jia ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Colony Formation ◽  
Noncoding Rna ◽  
Luciferase Reporter ◽  
Tumor Node Metastasis Stage

Abstract Background Emerging evidences have revealed that long non-coding RNAs (lncRNAs) have played critical roles in tumor occurrence and progression. LINC00641 has been reported to be involved in the initiation and development of several cancers in the recent years. However, the detailed biological role of LINC00641 in renal cell carcinoma (RCC) remains largely unclear. Methods In this study, the expression and biological function of LINC00641 were assessed in renal carcinoma both in vitro and in vivo. Cell proliferation, migration and colony formation assay were performed to explore the effect of LINC00641on growth, progression and invasion of RCC cell. qRT-PCR, flow cytometry and luciferase reporter assay and in vivo tumorigenicity assay were also carried out. Results The expression of LINC00641 was overexpressed in RCC tissues and cell lines, and high LINC00641 expression was correlated with tumor-node-metastasis stage. Furthermore, Silencing of LINC00641 remarkably inhibited the ability of cell proliferation, colony formation, and invasive capacities, as well as increasing the apoptotic rates of RCC cells in vitro. Mechanistically, miR-340-5p was validated to be targeted by LINC00641 and knockdown of miR-340-5p counteracted LINC00641 silencing-mediated inhibition of RCC progression. In addition, in vivo experiment confirmed the findings discovered in vitro. Conclusions These results suggested that LINC00641 promoted the progression of RCC by sponging miR-340-5p.

scholarly journals Blocking Exosomal miR-19b-3p from Renal Cell Carcinoma Cells Enhances Sunitinib Mediated Anti-Tumor Activity via Promoting TGFBR2/KLF10 Expression

2021 ◽  
Author(s):  
Dong Lv ◽  
Taimin Shen ◽  
Juncheng Yao ◽  
Qi Yang ◽  
Ying Xiang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Resistant Cell ◽  
Cell Counting ◽  
Induced Apoptosis ◽  
Related Proteins

Abstract Background Multiple studies have found that microRNAs contribute to the malignant progression and chemoresistance of renal cell carcinoma (RCC). This study intends to probe the effect of miR-19b-3p shuttled by exosomes derived from RCC cells on RCC development and its resistance to Sunitinib. Methods Sunitinib-resistant cell lines (OSRC-2R and Caki-1R) were constructed from OSRC-2 and Caki-1 RCC cells. Exosomes in the RCC cell supernatant were isolated, and the miR-19b-3p profile in cells and exosomes was measured by reverse transcription-polymerase chain reaction (RT-PCR). Subsequently, the TGFβR2/SMAD2/3 pathway was activated by TGFβ, and the KLF10 overexpression and miR-19b-3p overexpression/knockdown models were constructed. The cell counting kit-8 (CCK-8) assay, colony formation assay and flow cytometry were implemented to verify RCC cell proliferation, Sunitinib chemosensitivity, and apoptosis. The expression of apoptosis-related proteins and the TGFβR2-SMAD2/3-KLF10 pathway was monitored by Western blot. MiR-19b-3p was overexpressed in sunitinib-resistant RCC cell lines (OSRC-2R and Caki-1R) and their exosomes (vs. normal OSRC-2 and Caki-1 cell lines). Results In-vitro experiments showed that knocking down cellular and exosomal miR-19b-3p levels reduced the proliferation and colony-forming ability of OSRC-2 and Caki-1 cells and strengthened their apoptosis and sensitivity to Sunitinib. Bioinformatics analysis illustrated that miR-19b-3p targeted TGFβR2 and inhibited TGFβR2/SMAD2/3. Activation of the TGFβR2-SMAD2/3 pathway via TGFβ dampened ORSC-2 and Caki-1 cell proliferation, induced apoptosis, and enhanced their chemosensitivity to Sunitinib. Conclusion Moreover, TGFβ heightened KLF10 expression, and overexpressing KLF10 attenuated miR-19b-3p-mediated carcinogenic effects and resistance to Sunitinib by increasing SMAD2/3 phosphorylation. RCC cell-derived exosomal miR-19b-3p enhances RCC progression and Sunitinib chemoresistance by inactivating TGFβR2-SMAD2/3-KLF10.

scholarly journals miR-331-3p Inhibits Proliferation and Promotes Apoptosis of Nasopharyngeal Carcinoma Cells by Targeting elf4B-PI3K-AKT Pathway

2020 ◽  
Vol 19 ◽  
pp. 153303381989225 ◽  
Author(s):  
Zhang Xuefang ◽  
Zheng Ruinian ◽  
Jiang Liji ◽  
Zhang Chun ◽  
Zheng Qiaolan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Nasopharyngeal Carcinoma ◽  
Cell Apoptosis ◽  
Target Gene ◽  
Regulation Of Gene Expression ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Clinical Samples ◽  
Phosphoinositide 3 Kinase

Background: The incidence of nasopharyngeal carcinoma is increasing gradually, but the pathogenesis is not completely clear. MicroRNA, a highly conserved endogenous noncoding small molecule RNA, plays an essential role in the regulation of gene expression and is a hotspot in cancer research worldwide. Objectives: Although previous studies have confirmed that the abnormal expression of microRNAs is closely related to the progression of nasopharyngeal carcinoma, the role of miRNA-331-3p in nasopharyngeal carcinoma has not been studied. The purpose of this study was to explore the role and mechanism of miRNA-331-3p in the progression of nasopharyngeal carcinoma. Materials and Methods: Real-time quantitative reverse transcription polymerase chain reaction was performed to detect the expression of miRNA-331-3p in nasopharyngeal carcinoma clinical samples and cell lines (CNE-1 and 5-8F cells). After overexpression of miRNA-331-3p in CNE-1 cells, cell proliferation was measured by Cell Counting Kit-8 assay, cell invasion was detected by Transwell assay, and apoptosis was tested by flow cytometry. In addition, the dual-luciferase reporter assay was used to identify the target gene of miRNA-331-3p and Western blotting was performed to measure the relative protein expression. Results: The expression of miRNA-331-3p in nasopharyngeal carcinoma clinical samples and cells was decreased significantly. Overexpression of miRNA-331-3p markedly inhibited the proliferation and invasion of CNE-1 cells and promoted cell apoptosis. Moreover, overexpression of miRNA-331-3p reduced the expression of target gene elF4B, leading to inhibition of the phosphorylation of Phosphoinositide 3-kinase (PI3K) and Serine/ threonine kinase (AKT). Conclusion: miRNA-331-3p inhibited cell proliferation and induced cell apoptosis in nasopharyngeal carcinoma by targeting elF4B gene and then blocked the PI3K-AKT signaling pathway. Significance: The role of miRNA-331-3p in the development of NPC and its mechanism provide new ideas for the treatment of nasopharyngeal carcinoma.

scholarly journals miR-198 inhibits the progression of renal cell carcinoma by targeting BIRC5

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chao Yuan ◽  
Zhenhong Su ◽  
Shengjie Liao ◽  
Duanzhuo Li ◽  
Zhiwen Zhou ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Mouse Model ◽  
Cell Carcinoma ◽  
Nude Mouse ◽  
Renal Cell ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mrna Levels ◽  
Nude Mouse Model

Abstract Background miR-198 is involved in the formation, migration, invasion, and metastasis of various malignant cancers. However, the function and mechanism of action of miR-198 in the tumorigenesis of renal cell carcinoma (RCC) remain elusive. Here, we aimed to explore the role of miR198 in RCC. Methods Immunohistochemistry was performed to estimate the level of survivin in RCC sections. Quantitative real-time polymerase chain reaction was performed to determine the expression level of miR-198 in fresh RCC tissues. Furthermore, the target relationship between miR-198 and BIRC5 was predicted using the TargetScanHuman 7.2 database and verified via dual-luciferase reporter assay and western blotting. The effects of miR-198 on the viability, apoptosis, invasion, and migration of A498 and ACHN cells were studied using Cell Counting Kit-8, flow cytometry, transwell migration assay, and wound healing assay, respectively. Additionally, a xenograft nude mouse model was established to evaluate the effect of miR-198 on RCC tumorigenesis. Results The expression levels of BIRC5 and miR-198 were respectively higher and lower in RCC tissues than those in normal adjacent tissues. Furthermore, miR-198 could inhibit luciferase activity and reduce the protein level of survivin without affecting the BIRC5 mRNA levels. miR-198 inhibited cell viability, migration, and invasion and promoted cell apoptosis; co-transfection with BIRC5 could rescue these effects. Moreover, miR-198 could repress tumor growth in the xenograft nude mouse model of RCC. Conclusions Our study demonstrates that miR-198 suppresses RCC progression by targeting BIRC5.

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