&lt;p&gt;Lipase member H is a downstream molecular target of hypoxia inducible factor-1&amp;alpha; and promotes papillary thyroid carcinoma cell migration in BCPAP and KTC-1 cell lines&lt;/p&gt;

Li, Yuefeng; Zhou, Xiaofen; Zhang, Qiongying; Chen, Endong; Sun, Yihan; Ye, Danrong; Wang, Ouchen; Zhang, Xiaohua; Lyu, Jianxin

doi:10.2147/cmar.s183355

Cited by 12 publications

(10 citation statements)

References 26 publications

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“…Our data exhibited that Twist1 was dropped and E-cadherin was raised after circ_LDLR deficiency in PTC cells. LIPH has been demonstrated to be increased in PTC, and LIPH knockdown suppressed PTC cell colony formation, proliferation and metastasis [20]. Here, we confirmed that LIPH was a target gene of miR-195-5p.…”

Section: Discussionsupporting

confidence: 76%

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Circ_LDLR promoted the development of papillary thyroid carcinoma via regulating miR-195-5p/LIPH axis

Gui

Zhang

et al. 2020

Preprint

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Background: Emerging studies have demonstrated that circular RNAs (circRNAs) are key regulators for tumorigenesis in cancers, including papillary thyroid carcinoma (PTC). In this study, we attempted to explore the effects of circ_LDLR on PTC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was adopted to determine the levels of circ_LDLR, miR-195-5p and lipase H (LIPH). RNase R digestion assay and Actinomycin D assay were utilized to analyze the characteristics of circ_LDLR. Colony formation assay and 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay were employed to evaluate cell proliferation. Western blot assay was used for the determination of protein levels. Flow cytometry analysis was applied to determine cell apoptosis. Transwell assay was performed to assess cell migration and invasion. Dual-luciferase reporter assay was used to verify the associations among circ_LDLR, miR-195-5p and LIPH. The murine xenograft model was constructed to explore the roles of circ_LDLR in vivo . Results: Compared to normal tissues and cells, circ_LDLR was upregulated in PTC tissues and cells. Silencing of circ_LDLR suppressed PTC cell colony formation, proliferation, migration and invasion and promoted apoptosis in vitro and hampered tumor growth in vivo. For mechanism investigation, circ_LDLR could regulate LIPH expression via sponging miR-195-5p. Moreover, miR-195-5p inhibition restored the effects of circ_LDLR knockdown on the malignant behaviors of PTC cells. MiR-195-5p overexpression inhibited PTC cell colony formation, proliferation, migration and invasion and facilitated apoptosis by targeting LIPH. Conclusion: Circ_LDLR knockdown decelerated PTC progression by regulating miR-195-5p/LIPH axis, which might provide a novel therapeutic target for PTC.

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Section: Discussionsupporting

confidence: 76%

“…Cui et al declared that LIPH was associated with the tumor size, lymph node metastasis, and distant metastasis of breast cancer [19]. Moreover, a previous study demonstrated that LIPH could aggravate PTC development [20]. However, the underlying mechanisms of LIPH in PTC are not entirely understood.…”

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confidence: 99%

Circ_LDLR promoted the development of papillary thyroid carcinoma via regulating miR-195-5p/LIPH axis

Gui

Zhang

et al. 2020

Preprint

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“…31 It was reported that hypoxia-inducible factor-1α (HIF-1α) gene expression was increased during hypoxic conditions in tumors, including PTC. 32 Furthermore, ANGPTL4 is known to be a gene induced by hypoxia. Studies have shown that HIF-1α directly up-regulated the expression of ANGPTL4 in hepatocellular carcinoma cells.…”

Section: Discussionmentioning

confidence: 99%

<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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“…LIPH is a member of the mammalian triglyceride lipase family. The expression of LIPH was found to be involved in papillary thyroid carcinoma development (54) and mRNA level of LIPH may act as a prognostic marker for esophageal adenocarcinoma, lung cancer and breast cancer (55)(56)(57). Study demonstrated that CIRH1A plays regulatory roles in proliferation and apoptosis of colorectal cancer cell (58).…”

Section: Liphmentioning

confidence: 97%

Investigation on Gastric Cancer Susceptibility Genes in Chinese Early-onset Diffuse Gastric Cancer

Feng

Zhang

et al. 2020

Preprint

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Abstract BackgroundDiffuse gastric cancer (DGC) is known as gastric cancer with diffuse type morphology. Early onset DGC is an indicator of suspicious hereditary diffuse gastric cancer (HDGC). HDGC patient are often less sensitive to chemotherapy and suffer from highly invasive late stage malignancy with poor prognosis. Such hereditary cancer syndrome is closely related to deleterious CDH1 germline variant. In addition, potential pathogenic germline variants in other candidate genes were also observed in HDGC families. However, the profile of gastric cancer (GC) susceptibility gene in Chinese HDGC patients is yet to be elucidated.MethodsTo investigate gastric cancer susceptibility genes in Chinese gastric cancer patients, we collected peripheral blood samples from 29 patients fulfilled both HDGC clinical diagnosis and genetic testing criteria updated on 2015 by IGCLC. Genomic DNA was extracted from peripheral blood followed by Whole Exome Sequencing (WES) with average sequencing depth of at least 100X. Gastric cancer predisposing SNV and Indel candidates were filtered based on population allele frequencies in public nucleotide polymorphism databases and pathogenic variant filtering process was performed to identify potential gastric cancer predisposing variant candidates. Immunohistochemistry was conducted on biopsies from patient who carries potential pathogenic CDH1 germline variant.ResultsIn general, 336296 germline non-synonymous variants were detected from 29 GC patients. According to the pathogenic variant filtering process, 25 germline variant candidates in 22 genes were identified as gastric cancer predisposing variant candidates. In addition, a novel splice-site variant, c.2165-1G>A (NM_004360.4), in CDH1 was detected in a Chinese early-onset HDGC patient who developed ovarian metastasis. Furthermore, IHC analysis on the ovarian cancer tissue from this patient demonstrated weakly to moderate staining of E-cadherin compared with positive control. Moreover, another two variants, CTNNA1 c.1975_1976del (NM_001903.2), APC c.-19+1G>A (NM_001127511.2), were suspicious of gastric cancer predisposing variants.ConclusionsThis study suggested that CDH1 c.2165-1G>A may act as a gastric cancer predisposing variant. In addition, to further investigate molecular mechanisms of early-onset gastric cancer, one may consider 22 genes observed in this study. Furthermore, the inconclusive results in this study warrant future investigation on gastric cancer susceptibility gene discovery that cohort selection may require more stringent conditions.

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<p>Lipase member H is a downstream molecular target of hypoxia inducible factor-1α and promotes papillary thyroid carcinoma cell migration in BCPAP and KTC-1 cell lines</p>

Cited by 12 publications

References 26 publications

Circ_LDLR promoted the development of papillary thyroid carcinoma via regulating miR-195-5p/LIPH axis

Circ_LDLR promoted the development of papillary thyroid carcinoma via regulating miR-195-5p/LIPH axis

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

Investigation on Gastric Cancer Susceptibility Genes in Chinese Early-onset Diffuse Gastric Cancer

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