PATHOLOGY RESEARCH AND PRACTICE
·
2020
·
IF 2.05
Jianfa Wu,Li Zhang,Suqin Wu,Xiaofang Yi,Zhou Liu
Background miR-194-5p has been associated with drug resistance in many cancers. However, the role of miR-194-5p in cisplatin resistance in ovarian cancer is still unclear. Materials and methods To study the role and mechanism of miR-194-5p in cisplatin resistance, qRT-PCR was performed to determine the expression of miR-194-5p and SLC40A1 in ovarian cancer. Cell Counting Kit-8 (CCK8) assay was used to analyse cell viability after cisplatin treatment . Dual-luciferase reporter gene assay was performed to examine the relationship between miR-194-5p and SLC40A1. The genes downstream of SLC40A1 were investigated through bioinformatics analysis. Results Compared to cisplatin-sensitive ovarian cancer cells , higher miR-194-5p expression and lower SLC40A1 expression were found in cisplatin-resistant ovarian cancer cells. Moreover, this study demonstrated that over-expression of miR-194-5p inhibited SLC40A1 expression, and knockdown of miR-194-5p promoted SLC40A1 expression. In addition, dual-luciferase reporter gene assay further confirmed the negative correlation between miR-194-5p and SLC40A1. Furthermore, we found that over-expression of miR-194-5p resulted in cisplatin resistance. When miR-194-5p and SLC40A1 were simultaneously up-regulated, cisplatin sensitivity increased, while down-regulation of miR-194-5p sensitised ovarian cancer cells to cisplatin. However, when miR-194-5p and SLC40A1 were simultaneously down-regulated, cisplatin sensitivity was decreased. These data suggested that miR-194-5p inhibited SLC40A1 expression to induce cisplatin resistance. In addition, bioinformatics analysis indicated a positive correlation of SLC40A1 with hephaestin (HEPH), and homeostatic iron regulator (HFE). However, we found that HEPH and HFE were associated with cisplatin resistance, suggesting that their role in drug resistance is induced by miR-194-5p/SLC40A1. Conclusion In conclusion, we found that miR-194-5p inhibited SLC40A1 expression to induce cisplatin resistance in ovarian cancer. This study suggests that miR-194-5p could be a potential therapeutic target and a prognostic biomarker for ovarian cancer, with important implications for future research.
研究领域:
肿瘤学
·
分子生物学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2021
·
IF 6.244
Yang Jianru,Jia Yang,Wang Bing,Yang Shengrong,Du Kun,Luo Yujie,Li Yunhe,Zhu Bing
Background: The effects of up-regulated CircCHST15 on lung cancer remained unclear. In this study, the role of CircCHST15 in lung cancer was investigated.Methods: Dual-luciferase reporter verified the bioinformatics prediction that CircCHST15 targeted miR-155-5p and miR-194-5p. The correlation between CircCHST15 and PD-L1 was analyzed by Pearson analysis. CCK-8 and colony formation was performed to determine the viability and proliferation of lung cancer cells. After the lung cancer (subcutaneous-xenotransplant) model was established in mice, the T cell subtype and related cytokines in mouse tumor tissues were detected by flow cytometry and ELISA. Moreover, the expressions of CircCHST15, miR-155-5p, miR-194-5p, immune-related, and proliferation-related factors of the lung cancer cells or mice tumor tissues were detected by immunohistochemistry, RT-qPCR, or Western blot.Results: CircCHST15 and PD-L1 were high-expressed in lung cancer, and the two was positively correlated. CircCHST15 targeted miR-155-5p and miR-194-5p, the later further targeted PD-L1. Lung cancer cell viability and proliferation were increased by miR-155-5p and inhibited by miR-194-5p. CircCHST15 located in the cytoplasm promoted tumor growth, down-regulated the expressions of miR-155-5p and miR-194-5p, and up-regulated the expressions of PD-L1, Ki-67, PCNA, CCL17, CCL22, IFN-γ, TNF-β, and IL-10. Also, CircCHST15 decreased the CD8+ cells in mouse blood and tumor, but increased the Tregs in mouse tumor. PD-L1 inhibitor showed an opposite effect to CircCHST15 on mouse tumors.Conclusion: CircCHST15 sponged miR-155-5p and miR-194-5p to promote the PD-L1-mediated immune escape of lung cancer cells.
研究领域:
肿瘤学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANNALS OF CLINICAL AND LABORATORY SCIENCE
·
2022
·Vol. 52
·期 5
·707-720
·
IF 1.18
Xiaowei Lu,Kui Hu,Qunya Tan,Kai Zhao
Objective Long non-coding RNA small nuclear host gene 1 (LncRNA SNHG1) was implicated in several malignancies, but its role and interactionwith microRNAs (miRs) in gallbladder cancer (GBC) were awaited to be addressed. Methods Clinical GBC tissues were collected. After transfection, GBC cell viability, proliferation and invasion were determined byMTT assay, colony formation assay and Transwell assay, respectively. Target gene and potential binding sites were predicted,followed by confirmation with dual-luciferase reporter assay. Relative expressions of SNHG1, miR-194-5p, epithelial-mesenchymaltransition (EMT)-related markers, LIF interleukin 6 family cytokine (LIF), stathmin1 (STMN1), platelet derived growth factorsubunit A (PDGFA), insulin like growth factor 1 receptor (IGF1R) and signal transducer and activator of transcription 1 (STAT1)were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot as needed. Correlation betweenSNHG1 and miR-194-5p in GBC was analyzed. Results High expression of SNHG1 was observed in both GBC tissues and cells, and it was associated with tumor sizes. ShSNHG1 inhibitedSNHG1 expression and retarded the viability, proliferation and invasion of GBC cells, accompanied with downregulated N-Cadherinand Vimentin yet upregulated E-Cadherin. MiR-194-5p could competitively bind with SNHG1 and was low-expressed in GBC, revealingthe negative correlation between SNHG1 and miR-194-5p. Downregulated miR-194-5p reversed the effects of SNHG1 silencing onviability, proliferation, invasion and EMT-related marker expressions in GBC cells. Additionally, LIF and PDGFA were the targetgenes of miR-194-5p. Conclusions SNHG1 silencing suppressed the viability, proliferation and invasion of GBC cells via targeting miR-194-5p, revealing a newrole of SNHG1 in GBC.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
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