scholarly journals Silencing long non-coding RNA ROR improves sensitivity of non-small-cell lung cancer to cisplatin resistance by inhibiting PI3K/Akt/mTOR signaling pathway

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769756 ◽  
Author(s):  
Hui Shi ◽  
Jin Pu ◽  
Xiao-Li Zhou ◽  
Yun-Ye Ning ◽  
Chong Bai
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Negative Control ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Control Groups ◽  
Over Expression ◽  
Non Coding Rna ◽  
Protein Expressions ◽  
Long Non Coding Rna

This study aimed to investigate the effects of long non-coding RNA ROR (regulator of reprogramming) on cisplatin (DDP) resistance in patients with non-small-cell lung cancer by regulating PI3K/Akt/mTOR signaling pathway. Human cisplatin-resistant A549/DDP cell lines were selected and divided into control group, negative control group, si-ROR group, ROR over-expression group, Wortmannin group, and ROR over-expression + Wortmannin group. MTT assay was used to determine the optimum inhibitory concentration of DDP. Quantitative real-time polymerase chain reaction and western blotting were applied to detect expressions of long non-coding RNA ROR, PI3K, Akt, and mTOR. Colony-forming assay, scratch test, Transwell assay, and flow cytometry were conducted to detect cell proliferation, migration, invasion, and apoptosis, respectively. Tumor-formation assay was performed to detect the growth of transplanted tumors. Long non-coding RNA ROR expression was high in human A549/DDP cell lines. Compared with the control and negative control groups, the mRNA and protein expressions of PI3K, Akt, mTOR, and bcl-2 decreased, whereas the mRNA and protein expression of bax and the sensitivity of cells to DDP significantly increased. Cell proliferation, migration, and invasion abilities decreased in the si-ROR and Wortmannin groups. In comparison with control and negative control groups, the mRNA and protein expressions of PI3K, Akt, mTOR, and bcl-2 increased, whereas the mRNA and protein expressions of bax decreased, the sensitivity of cells to DDP significantly increased, and cell proliferation, migration, and invasion abilities decreased in the ROR over-expression group. For nude mice in tumor-formation assay, compared with control and negative control groups, the tumor weight was found to be lighter (1.03 ± 0.15) g, the protein expressions of PI3K, Akt, mTOR, and bcl-2 decreased, and the protein expression of bax increased in the si-ROR group. Long non-coding RNA ROR may affect the sensitivity of lung adenocarcinoma cells to DDP by targeting PI3K/Akt/mTOR signaling pathway.

scholarly journals The Long Non-Coding RNA CRNDE Promotes Colorectal Carcinoma Progression by Competitively Binding miR-217 with TCF7L2 and Enhancing the Wnt/β-Catenin Signaling Pathway

2017 ◽  
Vol 41 (6) ◽  
pp. 2489-2502 ◽  
Author(s):  
Bo Yu ◽  
Xuan Ye ◽  
Qiong Du ◽  
Bin Zhu ◽  
Qing Zhai
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Migration And Invasion ◽  
Down Regulation ◽  
Over Expression ◽  
Non Coding Rna ◽  
Colorectal Cancer Cells ◽  
Long Non Coding Rna

Background/Aims: The long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) contributes to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer remains unknown. In the present study, we investigated whether CRNDE was involved in the development of colorectal cancer via the binding of microRNA (miR)-217 with transcription factor 7-like 2 (TCF7L2) to enhance the Wnt signaling pathway. Methods: Quantitative polymerase chain reaction was used to detect CRNDE, miR-217 and TCF7L2 in colorectal cancer tissues and cells. The CCK-8 assay, wound healing assay, and Transwell assay were used to detect cell proliferation, migration and invasion, respectively. Western blotting and luciferase activity assays were used to identify CRNDE and TCF7L2 as one of the direct targets of miR-217. The activity of the Wnt/β-catenin signaling pathway was analyzed by the TOPflash assay, and the subcellular localization of β-catenin and TCF7L2 was analyzed by western blotting and confocal microscopy. Results: In this study, we found that high expression of CRNDE is negatively correlated with low expression of miR-217 in colorectal cancer tissue and colorectal cancer cells. The dual luciferase reporter analysis showed that miR-217 is bound to CRNDE and TCF7L2 and negatively regulate their expression. CRNDE down-regulation inhibited the cell proliferation, migration and invasion in vitro and in vivo and the inhibitions were both completely blocked after miR-217 inhibition or TCF7L2 overexpression. Finally, TOPflash analysis showed that the activity of Wnt/β-catenin signaling is inhibited by CRNDE down-regulation and rescued by TCF7L2 over-expression. Consistently immunostaining and western blotting analysis showed that the expression of b-catenin and TCF7L2 in the nucleus was significantly decreased by CRNDE down-regulation and was rescued by TCF7L2 over-expression. Conclusions: The present study suggest that CRNDE involves in the cell proliferation, migration and invasion of colorectal cancer cells via increasing the expression of TCF7L2 and activity of Wnt/β-catenin signaling through binding miR-217 competitively.

Long non-coding RNA tumor protein 53 target gene 1 promotes cervical cancer development via regulating microRNA-33a-5p to target forkhead box K2 (Preprint)

2021 ◽  
Author(s):  
Yanyan Liu Sr ◽  
xiaomei Liu ◽  
xiuying Yuan ◽  
poling Feng ◽  
zhiwei Ouyang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Signaling Pathway ◽  
Target Gene ◽  
Mtor Signaling ◽  
Regulatory Function ◽  
Clinical Samples ◽  
Mtor Signaling Pathway ◽  
Forkhead Box ◽  
Non Coding Rna ◽  
Long Non Coding Rna

BACKGROUND Long non-coding RNA tumor protein 53 target gene 1 (TP53TG1) has been studied in multiple diseases, while the regulatory function of TP53TG1 on cervical cancer (CC) via regulating microRNA (miR)-33a-5p to target Forkhead box K2 (FOXK2) remains limited. This study aims to unearth the effects of TP53TG1/miR-33a-5p/FOXK2 axis on CC. OBJECTIVE This study aims to unearth the effects of TP53TG1/miR-33a-5p/FOXK2 axis on CC. METHODS The clinical samples were collected and TP53TG1, miR-33a-5p and FOXK2 levels were examined in CC tissues. The CC cells were transfected with high- or low-expressed TP53TG1, FOXK2 and miR-33a-5p to determine the change of CC cell biological activities and the status of phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. The tumorigenesis in nude mice was conducted. The relationship among TP53TG1, miR-33a-5p and FOXK2 was validated. RESULTS TP53TG1 and FOXK2 were enriched and miR-33a-5p was inhibited in CC. The reduced TP53TG1 or FOXK2 or elevated miR-33a-5p decelerated the CC cell development and the activation of PI3K/AKT/mTOR signaling pathway. The depleted FOXK2 or enriched miR-33a-5p reversed the effects of decreased TP53TG1. TP53TG1 sponged miR-33a-5p which targeted FOXK2. The experiment in vivo validated the outcomes of the experiment in vitro. CONCLUSIONS TP53TG1 accelerates the CC development via regulating miR-33a-5p to target FOXK2 with the involvement of PI3K/AKT/mTOR signaling pathway. This study provides novel theory references and a distinct direction for the therapy strategies of CC.

scholarly journals Upregulation of Long Noncoding RNA_GAS5 Suppresses Cell Proliferation and Metastasis in Laryngeal Cancer via Regulating PI3K/AKT/mTOR Signaling Pathway

2021 ◽  
Vol 20 ◽  
pp. 153303382199007
Author(s):  
Wenlin Liu ◽  
Jiandong Zhan ◽  
Rong Zhong ◽  
Rui Li ◽  
Xiaoli Sheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Laryngeal Cancer ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Proliferation And Metastasis ◽  
Cancer Tissues ◽  
Lncrna Gas5

Background: Laryngeal cancer is one of the most common malignant tumors among head and neck cancers. Accumulating studies have indicated that long noncoding RNAs (lncRNAs) play an important role in laryngeal cancer occurrence and progression, however, the functional roles and relative regulatory mechanisms of lncRNA growth arrest-specific transcript 5 (GAS5) in laryngeal cancer progression remain unclear. Methods: The expression of lncRNA GAS5 in both laryngeal cancer tissues and cell lines was evaluated using quantitative reverse transcription-polymerase chain reaction (RT-qPCR) assay. The relationships between lncRNA GAS5 expression and clinical parameters were also analyzed. To determine the biological function of lncRNA GAS5, a lncRNA GAS5-specific plasmid was first transfected into laryngeal cancer cells using lentiviral technology. Cell counting kit-8 assay, flow cytometry, and Transwell assays were used to detect in vitro cell proliferation, apoptosis, cycle distribution, and metastasis abilities, respectively. Furthermore, in vivo cell growth experiments were also performed using nude mice. Additionally, western blotting was performed to identify the underlying regulatory mechanism. Results: In the current study, lncRNA GAS5 was downregulated in laryngeal cancer tissues and its low expression was closely associated with poor tumor differentiation, advanced TNM stage, lymph node metastasis, and shorter overall survival time. In addition, lncRNA GAS5 upregulation significantly inhibited laryngeal cancer cell proliferation both in vitro and in vivo. Moreover, in response to lncRNA GAS5 overexpression, more laryngeal cancer cells were arrested at the G2/M stage, accompanied by increased cell apoptosis rates and suppressed migration and invasion capacities. Mechanistically, our data showed that the overexpression of lncRNA GAS5 significantly regulated the PI3K/AKT/mTOR signaling pathway. Conclusion: LncRNA GAS5 might act as a suppressor gene during laryngeal cancer development, as it suppressed cell proliferation and metastasis by regulating the PI3K/AKT/mTOR signaling pathway; thus, lncRNA GAS5 is a promising therapeutic biomarker for the treatment of laryngeal cancer.

scholarly journals Kaempferol inhibits proliferation, migration, and invasion of liver cancer HepG2 cells by down-regulation of microRNA-21

2018 ◽  
Vol 32 ◽  
pp. 205873841881434 ◽  
Author(s):  
Genglong Zhu ◽  
Xialei Liu ◽  
Haijing Li ◽  
Yang Yan ◽  
Xiaopeng Hong ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Liver Cancer ◽  
Signaling Pathway ◽  
Hepg2 Cell ◽  
Cell Apoptosis ◽  
Hepg2 Cells ◽  
Mtor Signaling ◽  
Brdu Incorporation ◽  
Migration And Invasion ◽  
Mtor Signaling Pathway

Liver cancer is one of the most common and lethal cancers in human digestive system, which kills more than half a million people every year worldwide. This study aimed to investigate the effects of kaempferol, a flavonoid compound isolated from vegetables and fruits, on hepatic cancer HepG2 cell proliferation, migration, invasion, and apoptosis, as well as microRNA-21 (miR-21) expression. Cell viability was detected using cell counting kit-8 (CCK-8) assay. Cell proliferation was measured using 5-bromo-2′-deoxyuridine (BrdU) incorporation assay. Cell apoptosis was assessed using Guava Nexin assay. Cell migration and invasion were determined using two-chamber migration (invasion) assay. Cell transfection was used to change the expression of miR-21. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to analyze the expressions of miR-21 and phosphatase and tensin homologue (PTEN). Expression of key proteins involved in proliferation, apoptosis, migration, invasion, and phosphatidylinositol 3-kinase/protein kinase 3/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway were evaluated using western blotting. Results showed that kaempferol significantly inhibited HepG2 cell proliferation, migration, and invasion, and induced cell apoptosis. Kaempferol remarkably reduce the expression of miR-21 in HepG2 cells. Overexpression of miR-21 obviously reversed the effects of kaempferol on HepG2 cell proliferation, migration, invasion, and apoptosis. Moreover, miR-21 negatively regulated the expression of PTEN in HepG2 cells. Kaempferol enhanced the expression of PTEN and inactivated PI3K/AKT/mTOR signaling pathway in HepG2 cells. In conclusion, kaempferol inhibited proliferation, migration, and invasion of HepG2 cells by down-regulating miR-21 and up-regulating PTEN, as well as inactivating PI3K/AKT/mTOR signaling pathway.

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