Apatinib Inhibits Cell Proliferation and Induces Autophagy in Human Papillary Thyroid Carcinoma via the PI3K/Akt/mTOR Signaling Pathway

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.

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MicroRNA miR-106a-5p targets forkhead box transcription factor FOXC1 to suppress the cell proliferation, migration, and invasion of ectopic endometrial stromal cells via the PI3K/Akt/mTOR signaling pathway

Bioengineered ◽

10.1080/21655979.2021.1933679 ◽

2021 ◽

Vol 12 (1) ◽

pp. 2203-2213

Author(s):

Xinyue Zhou ◽

Zhenyu Chen ◽

Lipeng Pei ◽

Jingli Sun

Keyword(s):

Cell Proliferation ◽

Transcription Factor ◽

Signaling Pathway ◽

Stromal Cells ◽

Mtor Signaling ◽

Migration And Invasion ◽

Mtor Signaling Pathway ◽

Endometrial Stromal Cells ◽

Forkhead Box

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microRNA‐539 functions as a tumor suppressor in papillary thyroid carcinoma via the transforming growth factor β1/Smads signaling pathway by targeting secretory leukocyte protease inhibitor

Journal of Cellular Biochemistry ◽

10.1002/jcb.28374 ◽

2019 ◽

Vol 120 (6) ◽

pp. 10830-10846 ◽

Cited By ~ 5

Author(s):

Cheng‐Bi Xu ◽

Xue‐Shi‐Bo‐Jie Liu ◽

Jin‐Qiu Li ◽

Xue Zhao ◽

Ding Xin ◽

...

Keyword(s):

Growth Factor ◽

Papillary Thyroid Carcinoma ◽

Tumor Suppressor ◽

Thyroid Carcinoma ◽

Protease Inhibitor ◽

Signaling Pathway ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β1 ◽

Secretory Leukocyte Protease Inhibitor ◽

Papillary Thyroid

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Validation of MicroRNA-188-5p Inhibition Power on Tumor Cell Proliferation in Papillary Thyroid Carcinoma

Cell Transplantation ◽

10.1177/0963689720918300 ◽

2020 ◽

Vol 29 ◽

pp. 096368972091830 ◽

Cited By ~ 1

Author(s):

Ping Zhou ◽

Andrew Irving ◽

Huifang Wu ◽

Juan Luo ◽

Johana Aguirre ◽

...

Keyword(s):

Cell Proliferation ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Tumor Cell ◽

Cellular Proliferation ◽

Tumor Cell Proliferation ◽

Papillary Thyroid ◽

Tumor Tissues ◽

Potential Biomarker ◽

And Function

Given the crucial role of microRNAs in the cellular proliferation of various types of cancers, we aimed to analyze the expression and function of a cellular proliferation-associated miR-188-5p in papillary thyroid carcinoma (PTC). Here we demonstrate that miR-188-5p is downregulated in PTC tumor tissues compared with the associated noncancerous tissues. We also validate that the miR-188-5p overexpression suppressed the PTC cancer cell proliferation. In addition, fibroblast growth factor 5 (FGF5) is observed to be downregulated in the PTC tumor tissues compared with the associated noncancerous tissues. Subsequently, FGF5 is identified as the direct functional target of miR-188-5p. Moreover, the silencing of FGF5 was found to inhibit PTC cell proliferation, which is the same pattern as miR-188-5p overexpression. These results suggest that miR-188-5p-associated silencing of FGF5 inhibits tumor cell proliferation in PTC. It also highlights the importance of further evaluating miR-188-5p as a potential biomarker and therapy target in PTC.

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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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