PI3K inhibitors IC87114 inhibits the migration and invasion of thyroid cancer cell in vitro and in vivo

YWHAE gene product belongs to the 14-3-3 protein family that mediates signal transduction in plants and mammals. Protein-coding and non-coding RNA (lncRNA) transcripts have been reported for this gene in human. Here, we aimed to functionally characterize YWHAE-encoded lncRNA in colorectal cancer-originated cells. RNA-seq analysis showed that YWHAE gene is upregulated in colorectal cancer specimens. Additionally, bioinformatics analysis suggested that YWHAE lncRNA sponges miR-323a-3p and miR-532-5p that were predicted to target K-Ras 3′UTR sequence. Overexpression of YWHAE lncRNA resulted in upregulation of K-Ras gene expression, while overexpression of both miR-323a-3p and miR-532-5p had an inverse effect, detected by RT-qPCR. Consistently, western blot analysis confirmed that YWHAE lncRNA overexpression upregulated K-Ras/Erk1/2 and PI3K/Akt signaling pathways, while miR-323a-3p and miR-532-5p overexpression suppressed both pathways in HCT116 cells. Furthermore, dual luciferase assay validated the direct interaction of miR-323a-3p and miR-532-5p with K-Ras 3′UTR sequence and supported the sponging effect of YWHAE lncRNA over both miRNAs. These results suggested YWHAE lncRNA as an oncogene that exerts its effect through sponging miR-323a-3p and miR-532-5p and in turn, upregulates K-Ras/Erk1/2 and PI3K/Akt signaling pathways. Consistently, flow cytometry analysis, MTT assay and measuring cyclin D1 gene expression, confirmed the cell cycle stimulatory effect of YWHAE lncRNA, while miR-323a-3p and miR-532-5p showed an inhibitory effect on cell cycle progression. Finally, wound-healing assay supported the cell migratory effect of YWHAE lncRNA in HCT116 cells. This study identified a novel mechanism involving YWHAE-encoded lncRNA, miR-323a-3p and miR-532-5p in regulating HCT116 cell survival and suggested a potential therapeutic avenue for colorectal cancer.

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<p>ANGPTL4 Promotes the Proliferation of Papillary Thyroid Cancer via AKT Pathway</p>

Yang¹,

Wang²,

Sun³

et al. 2020

OTT

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Although papillary thyroid carcinoma (PTC) is associated with a generally favorable prognosis, about 15% of patients present recurrence and distant metastasis in the next decade leading to death. Angiopoietin-like 4 (ANGPTL4) is secreted to circulation and belongs to the angiopoietin-like proteins. The expression of ANGPTL4 was increased in several solid tumor tissues compared to corresponding paracancerous tissues. ANGPTL4 was identified as pro-tumorigenic protein, including stimulating tumor cell growth, promoting tumor metastasis. However, the clinical significance and biological function of ANGPTL4 in PTC is still unclear. Hence, the purpose of this study was to evaluate the role of ANGPTL4 in PTC, investigating the possibility of whether ANGPTL4 could become a novel target for PTC therapy. Methods: We investigated the expression level of ANGPTL4 and pAKT in PTC and paracancerous tissue by immunohistochemistry. We determined the effect of ANGPTL4 in PTC cell proliferation through cell counting kit-8 (CCK-8) and cell cycle by flow cytometry analysis. Furthermore, the correlation between ANGPTL4 expression levels and PTC cell proliferation from the TCGA data set was analyzed by GSEA. We explored the role of ANGPTL4 on the phosphorylation of AKT and proliferation in PTC cells via overexpression or knockdown assays and AKT inhibitor assay. Results: In the present study, we found that ANGPTL4 was highly expressed in both protein and mRNA level in PTC compared with adjacent noncancerous tissues or benign nodule. ANGPTL4 expression increased according to thyroid tumor progression. ANGPTL4 level was positively correlated with the size of PTC. ANGPTL4 increased cell proliferation and decreased cell cycle arrest of PTC. Knockdown of ANGPTL4 inhibited the phosphorylation of AKT. ANGPTL4 regulated PTC cell proliferation through AKT signaling pathway. Conclusion: Our findings suggested that ANGPTL4 was increased in PTC compared with adjacent noncancerous tissues, and ANGPTL4 increased cell proliferation and inhibited cell cycle arrest in PTC cells via promoting AKT phosphorylation. The study may provide fundamental information to suggest its suitability as a target for the treatment of PTC.

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PI3K inhibitors IC87114 inhibits the migration and invasion of thyroid cancer cell in vitro and in vivo

Cited by 3 publications

References 19 publications

Mouse models of thyroid cancer: Bridging pathogenesis and novel therapeutics

Mouse models of thyroid cancer: Bridging pathogenesis and novel therapeutics

YWHAE long non-coding RNA competes with miR-323a-3p and miR-532-5p through activating K-Ras/Erk1/2 and PI3K/Akt signaling pathways in HCT116 cells

<p>ANGPTL4 Promotes the Proliferation of Papillary Thyroid Cancer via AKT Pathway</p>

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