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Implication of hsa_circ_0028007 in reinforcing migration, invasion, and chemo-tolerance of nasopharyngeal carcinoma cells.

ABSTRACT: BACKGROUND:Given the reliability of circRNAs in symbolizing cancer progression, this investigation was designed to expound the involvement of hsa_circ_0028007 in regulating chemosensitivity of nasopharyngeal carcinoma (NPC) cells. METHODS:Altogether, 241 pairs of NPC tissues and para-cancerous normal tissues were collected to identify NPC-symbolic circRNAs, which have been screened by circRNA microarray in advance. Expressions of the circRNAs were determined by means of real-time polymerase chain reaction (PCR). Besides, human NPC cell lines (ie, CNE2 and HONE1) were transfected by si-hsa_circ_0028007 and si-NC. Scratch assay, transwell assay, and MTT assay were performed to assess migration, invasion, and paclitaxel/cisplatin-resistance of NPC cell lines. RESULTS:Hsa_circ_0028007 expression was abnormally heightened within NPC tissues in comparison with matched non-tumor tissues (P < .05). Over-expressed hsa_circ_0028007 was strongly associated with advanced (III-IV) tumor stage, aggressive infiltration, and metastatic lymph nodes of NPC patients (P < .05). Regarding in vitro experiments, hsa_circ_0028007 expression was elevated in CNE2 and HONE1 cell lines as compared with HENE cell line (P < .05). Silencing of hsa_circ_0028007 not merely sensitized CNE2 and HONE1 cells against paclitaxel and cisplatin (P < .05), but also significantly repressed migration and invasion of the cell lines (P < .05). CONCLUSION:Hsa_circ_0028007 was involved in facilitating progression and chemo-resistance of NPC, which might offer an alternative for NPC treatment.

SUBMITTER: Qiongna D

PROVIDER: S-EPMC7521330 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Implication of hsa_circ_0028007 in reinforcing migration, invasion, and chemo-tolerance of nasopharyngeal carcinoma cells.

Qiongna Dong D Jiafeng Zhang Z Yalin Hao H Ping He H Chuan Zhou Z Xiaojie Jin J Miaomiao Zhao Z Yiting Shao S Hui Zhao Z

Journal of clinical laboratory analysis 20200611 9

<h4>Background</h4>Given the reliability of circRNAs in symbolizing cancer progression, this investigation was designed to expound the involvement of hsa_circ_0028007 in regulating chemosensitivity of nasopharyngeal carcinoma (NPC) cells.<h4>Methods</h4>Altogether, 241 pairs of NPC tissues and para-cancerous normal tissues were collected to identify NPC-symbolic circRNAs, which have been screened by circRNA microarray in advance. Expressions of the circRNAs were determined by means of real-time ...[more]

PMID: 32524687

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Project description:Dickkopf-1 (DKK1), an inhibitor of the most frequently impaired signaling pathway in hepatocellular carcinoma (HCC), the Wnt/beta-catenin pathway, seems to fulfill contradictory functions in the process of tumorigenesis, acting either as an oncogenic promoter of metastasis or as a tumor suppressor. Elevated serum levels of DKK1 have been reported in HCC; however, little is known about its functional significance. In the current study, we treated HepG2/C3A and PLC/PRF/5 with the recombinant protein DKK1. Cytotoxicity was first determined by the WST-8 assay. AFP expression was measured at both the mRNA and protein levels. Expression of the oncogenes MYC, CCND1, hTERT, and MDM2 and the tumor suppressor genes TP53, P21 and RB was assessed. Western blot analysis of non-phosphorylated ẞ-catenin and Sanger sequencing were performed to explain the functional differences between the two cell lines. Subsequently, inflammation, migration and invasion were evaluated by qPCR, ELISA, the Boyden chamber assay, zymography, and MMP-2 and MMP-9 western blot analysis. Knockdown of DKK1 and TGF-β1 were also performed. Our results suggest that DKK1 exerts an oncogenic effect on HepG2/C3A cell line by upregulating the expression of oncogenes and downregulating that of tumor suppressor genes, whereas the opposite effect was demonstrated in PLC/PRF/5 cells. This differential impact of DKK1 can be explained by the mutations that affect the canonical Wnt pathway that were detected in exon 3 of the CTNNB1 gene in the HepG2 cell line. We further confirmed that DKK1 promotes inflammation, tumor invasion and migration in both cell types. The canonical pathway was not responsible for the DKK1 proinvasive effect, as indicated by the active ẞ-catenin levels in the two cell lines upon DKK1 treatment. Interestingly, knockdown of TGF-β1 negatively affected the DKK1 proinvasive effect. Taken together, DKK1 appears to facilitate tumor invasion and migration through TGF- β1 by remodeling the tumor microenvironment and inducing inflammation. This finding endorses the relevance of TGF-β1 as a therapeutic target.

Dataset Information

Implication of hsa_circ_0028007 in reinforcing migration, invasion, and chemo-tolerance of nasopharyngeal carcinoma cells.

Publications

Implication of hsa_circ_0028007 in reinforcing migration, invasion, and chemo-tolerance of nasopharyngeal carcinoma cells.

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