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)

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.

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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 ◽

10.1177/1010428317697568 ◽

2017 ◽

Vol 39 (5) ◽

pp. 101042831769756 ◽

Cited By ~ 31

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.

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Inhibition of Long Non-Coding RNA LOC100996425 Suppresses the Proliferation, Migration and Promotes Apoptosis of Prostate Cancer Cells Through the AMPK/mTOR Signaling Pathway by Targeting Hepatocyte Nuclear Factor 4A

SSRN Electronic Journal ◽

10.2139/ssrn.3372420 ◽

2019 ◽

Author(s):

Xing Hua ◽

Zhen Liu ◽

Min Zhou ◽

Yan Tian ◽

Pei-Pei Zhao ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Mtor Signaling ◽

Nuclear Factor ◽

Hepatocyte Nuclear Factor ◽

Mtor Signaling Pathway ◽

Prostate Cancer Cells ◽

Non Coding Rna ◽

Long Non Coding Rna

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Long Non-Coding RNA (lncRNA) Urothelial Carcinoma-Associated 1 (UCA1) Enhances Tamoxifen Resistance in Breast Cancer Cells via Inhibiting mTOR Signaling Pathway

Medical Science Monitor ◽

10.12659/msm.900689 ◽

2016 ◽

Vol 22 ◽

pp. 3860-3867 ◽

Cited By ~ 39

Author(s):

Chihua Wu ◽

Jing Luo

Keyword(s):

Breast Cancer ◽

Urothelial Carcinoma ◽

Cancer Cells ◽

Signaling Pathway ◽

Breast Cancer Cells ◽

Tamoxifen Resistance ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Non Coding Rna ◽

Long Non Coding Rna

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Long non-coding RNA HAGLROS regulates lipid metabolism reprogramming in intrahepatic cholangiocarcinoma via the mTOR signaling pathway

Experimental and Molecular Pathology ◽

10.1016/j.yexmp.2020.104466 ◽

2020 ◽

Vol 115 ◽

pp. 104466 ◽

Cited By ~ 1

Author(s):

Jun Ma ◽

Jinfeng Feng ◽

Xiang Zhou

Keyword(s):

Lipid Metabolism ◽

Signaling Pathway ◽

Intrahepatic Cholangiocarcinoma ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Non Coding Rna ◽

Long Non Coding Rna

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M2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathway

Journal of Translational Medicine ◽

10.1186/s12967-021-02766-w ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jie Yao ◽

Zefen Wang ◽

Yong Cheng ◽

Chao Ma ◽

Yahua Zhong ◽

...

Keyword(s):

Cell Migration ◽

Western Blot ◽

Signaling Pathway ◽

Target Gene ◽

Glioma Cells ◽

Mtor Signaling ◽

Migration And Invasion ◽

M2 Macrophage ◽

Mtor Signaling Pathway ◽

Cell Migration And Invasion

Abstract Background Glioma, the most common primary brain tumor, account Preparing figures for 30 to 40% of all intracranial tumors. Herein, we aimed to study the effects of M2 macrophage-derived exosomal microRNAs (miRNAs) on glioma cells. Methods First, we identified seven differentially expressed miRNAs in infiltrating macrophages and detected the expression of these seven miRNAs in M2 macrophages. We then selected hsa-miR-15a-5p (miR-15a) and hsa-miR-92a-3p (miR-92a) for follow-up studies, and confirmed that miR-15a and miR-92a were under-expressed in M2 macrophage exosomes. Subsequently, we demonstrated that M2 macrophage-derived exosomes promoted migration and invasion of glioma cells, while exosomal miR-15a and miR-92a had the opposite effects on glioma cells. Next, we performed the target gene prediction in four databases and conducted target gene validation by qRT-PCR, western blot and dual luciferase reporter gene assays. Results The results revealed that miR-15a and miR-92a were bound to CCND1 and RAP1B, respectively. Western blot assays demonstrated that interference with the expression of CCND1 or RAP1B reduced the phosphorylation level of AKT and mTOR, indicating that both CCND1 and RAP1B can activate the PI3K/AKT/mTOR signaling pathway. Conclusion Collectively, these findings indicate that M2 macrophage-derived exosomal miR-15a and miR-92a inhibit cell migration and invasion of glioma cells through PI3K/AKT/mTOR signaling pathway.

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