MiR-125b inhibits anaplastic thyroid cancer cell migration and invasion by targeting PIK3CD

Bu, Qingao; You, Faping; Pan, Guozheng; Yuan, Qing-Zhong; Tao, Cui; Long, Hao; Zhang, Jian

doi:10.1016/j.biopha.2016.11.090

Cited by 41 publications

(35 citation statements)

References 19 publications

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“…However, the other variants of the p110 catalytic subunit—β or δ—may be of importance and promote sustained activity of PI3K/AKT Ser473 and PI3K/AKT Thr308 despite PI3K110α inhibition. The δ isoform of the p110 catalytic subunit of PI3K has already shown anti-tumor potential in leukemia or in anaplastic thyroid carcinoma [ 66 , 67 ]. The theory of potential involvement of alternative PI3K subunit isoforms in NET signaling was supported by a much stronger inhibitory effect of the panPI3K inhibitor BKM120, compared to BYL719, on BON-1 cell viability (IC 20 BKM120 at 72h 0.5 μM vs. IC 20 BYL719 at 72h 6.9 μM; IC 50 BKM120 at 72h 1.2 μM vs. IC 50 BYL719 at 72h not reached).…”

Section: Discussionmentioning

confidence: 99%

The selective PI3Kα inhibitor BYL719 as a novel therapeutic option for neuroendocrine tumors: Results from multiple cell line models

et al. 2017

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Background/AimsThe therapeutic options for metastatic neuroendocrine tumors (NETs) are limited. As PI3K signaling is often activated in NETs, we have assessed the effects of selective PI3Kp110α inhibition by the novel agent BYL719 on cell viability, colony formation, apoptosis, cell cycle, signaling pathways, differentiation and secretion in pancreatic (BON-1, QGP-1) and pulmonary (H727) NET cell lines.MethodsCell viability was investigated by WST-1 assay, colony formation by clonogenic assay, apoptosis by caspase3/7 assay, the cell cycle by FACS, cell signaling by Western blot analysis, expression of chromogranin A and somatostatin receptors 1/2/5 by RT-qPCR, and chromogranin A secretion by ELISA.ResultsBYL719 dose-dependently decreased cell viability and colony formation with the highest sensitivity in BON-1, followed by H727, and lowest sensitivity in QGP-1 cells. BYL719 induced apoptosis and G0/G1 cell cycle arrest associated with increased p27 expression. Western blots showed inhibition of PI3K downstream targets to a varying degree in the different cell lines, but IGF1R activation. The most sensitive BON-1 cells displayed a significant, and H727 cells a non-significant, GSK3 inhibition after BYL719 treatment, but these effects do not appear to be mediated through the IGF1R. In contrast, the most resistant QGP-1 cells showed no GSK3 inhibition, but a modest activation, which would partially counteract the other anti-proliferative effects. Accordingly, BYL719 enhanced neuroendocrine differentiation with the strongest effect in BON-1, followed by H727 cells indicated by induction of chromogranin A and somatostatin receptor 1/2 mRNA-synthesis, but not in QGP-1 cells. In BON-1 and QGP-1 cells, the BYL719/everolimus combination was synergistic through simultaneous AKT/mTORC1 inhibition, and significantly increased somatostatin receptor 2 transcription compared to each drug separately.ConclusionOur results suggest that the agent BYL719 could be a novel therapeutic approach to the treatment of NETs that may sensitize NET cells to somatostatin analogs, and that if there is resistance to its action this may be overcome by combination with everolimus.

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Section: Discussionmentioning

confidence: 99%

The selective PI3Kα inhibitor BYL719 as a novel therapeutic option for neuroendocrine tumors: Results from multiple cell line models

et al. 2017

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“…Upregulation of miR-125b as an oncogene has been reported in various cancers: nasopharyngeal carcinoma (NPC), 13,14 retinoblastoma (RB), 15 glioblastoma (GBM), [16][17][18][19][20] poorly differentiated non-small-cell lung cancer (NSCLC), 21 acute lymphoblastic leukemia (ALL), 22 acute myeloid leukemia (AML), 23 and gastric cancer. [24][25][26] On the other hand, miR-125b, as a tumor suppressor, is downregulated in the following cancers: non-small-cell lung cancer (NSCLC), 27 esophageal squamous cell carcinoma (ESCC), 28,29 anaplastic thyroid cancer, 30 bladder cancer, [31][32][33][34][35] hepatocellular carcinoma (HCC), [36][37][38][39] melanoma, 40,41 ovarian cancer, [42][43][44] osteosarcoma, [45][46][47] chondrosarcoma, 48 breast cancer, [49][50][51][52][53][54][55] gallbladder cancer (GBC), 56 endometrioid endometrial cancer (EEC), 57 colorectal cancer (CRC), 58,…”

Section: Introductionmentioning

confidence: 99%

<p>The Emerging Roles of miR-125b in Cancers</p>

Wang¹,

Zeng²,

Jiang³

2020

CMAR

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MicroRNAs (miRNAs) are endogenous, noncoding, single-stranded RNA molecules of 22 nucleotides in length. MiRNAs have both tumor-suppressive properties and oncogenic properties that can control critical processes in tumors. Mature miR-125b originates from miR-125b-1 and miR-125b-2 and leads to the degradation of target mRNAs or the inhibition of translation through binding to the 3′ untranslated regions (3′-UTR) of target mRNAs. Importantly, miR-125b is involved in regulating NF-κB, p53, PI3K/Akt/mTOR, ErbB2, Wnt, and another signaling pathways, thereby controlling cell proliferation, differentiation, metabolism, apoptosis, drug resistance and tumor immunity. This review aims to summarize the recent literature on the role of miR-125b in the regulation of tumorigenesis and to explore its potential clinical application in the diagnosis, prognosis and clinical treatment of tumors.

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“…Of all miRNAs, >50% are known to be involved in human tumorigenesis by directly targeting oncogenes or tumor suppressor genes (3). For instance, miR-125b inhibits the tumor growth by directly targeting phosphatidylinositol-4.5-biphosphate 3-kinase catalytic subunit δ in ATC (4). Additionally, miR-4295 serves as an oncogene and promotes cell proliferation and invasion in ATC via cyclin dependent kinase inhibitor 1A (5).…”

Section: Introductionmentioning

confidence: 99%

miR‑544 inhibits the migration and invasion of anaplastic thyroid cancer by targeting Yin Yang‑1

Wang

Sun

2019

Oncol Lett

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Anaplastic thyroid cancer (ATC), with a mean survival time of 6 months, was reported in 2012 to account for 1-2% of all thyroid tumor cases in the US. Understanding the molecular mechanisms underlying carcinogenesis and progression in ATC would contribute to determining novel therapeutic targets. The aberrant expression of microRNA-544 (miR-544) has been demonstrated in various cancer types. However, its expression and biological function in human ATC remain largely unknown. Therefore, the present study investigated the expression, function and molecular mechanism of miR-544 in ATC. Results of reverse transcription-quantitative polymerase chain reaction demonstrated that the expression levels of miR-544 in 40 pairs of surgical specimens and human ATC cell lines were significantly decreased, compared with the normal thyroid tissues and cell line. Functional assays indicated that ectopic expression of miR-544 significantly decreased the viability, proliferation and metastasis of SW1736 cells, whereas miR-544 inhibitor significantly enhanced the viability, proliferation and metastasis of 8305C cells. Furthermore, the present study confirmed that the oncogene Yin Yang-1 (YY1) was a direct target of miR-544. It was further demonstrated that YY1 overexpression rescued the inhibitory effect of progression induced by miR-544 in ATC cells. Finally, in vivo study indicated that miR-544 suppressed the tumorigenicity of ATC cells. In conclusion, the present study demonstrated that miR-544 may function as a tumor suppressor in ATC and serve as a future therapeutic target for patients with ATC.

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MiR-125b inhibits anaplastic thyroid cancer cell migration and invasion by targeting PIK3CD

Cited by 41 publications

References 19 publications

The selective PI3Kα inhibitor BYL719 as a novel therapeutic option for neuroendocrine tumors: Results from multiple cell line models

The selective PI3Kα inhibitor BYL719 as a novel therapeutic option for neuroendocrine tumors: Results from multiple cell line models

<p>The Emerging Roles of miR-125b in Cancers</p>

miR‑544 inhibits the migration and invasion of anaplastic thyroid cancer by targeting Yin Yang‑1

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