Histology and histopathology Vol.38,nº10 (2023)

Ir a Estadísticas

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http://hdl.handle.net/10201/179836

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    Doxorubicin resistance in breast cancer xenografts and cell lines can be counterweighted by microRNA-140-3p, through PD-L1 suppression
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Zhang, Xia; Wang, Chao; Huang, Cuiping; Yang, Jianbao; Wang, Juan
    Background. Doxorubicin, a first-line chemotherapeutic drug for breast cancer, kills cancer cells by inducing DNA-crosslinking damage. Dysregulated micro-RNA (miRNA) is associated with the drug resistance of tumors. However, little is known about the effect of miRNA-140-3p on DOX resistance of breast cancer. Methods. The miRNA microarray was used to sequence the transcripts of DOX-chemoresistant breast cancer tissues and DOX-chemosensitive tissues. Then, the breast cancer tissue chip in the GEO database was also analyzed to screen the target gene. Flow cytometry, in situ hybridisation (ISH), immunohistochemistry (IHC), Western blot, cell proliferation assay, real-time PCR analyses (qRT-PCR), and pull-down assay were used to explore the effects of miRNA-140-3p and programmed death ligand-1 (PD-L1) on the chemoresistance of DOX-resistant breast cancer cells treated with DOX. In vivo, the DOX-resistant breast cancer cell lines treated with miRNA-140-3p overexpression were injected subcutaneously into mice to construct breast cancer subcutaneous xenograft tumor models. Results. Based on miRNA microarray, GEO database, and bioinformatics analysis, it was found that miRNA-140-3p and PD-L1 are the core molecules in the DOX resistance regulatory network in breast cancer, and lower miRNA-140-3p and higher PD-L1 expression levels were observed in DOX-resistant breast cancer tissues and cells. IHC results showed that compared with breast cancer tissues with high miRNA-140-3p expression, PD-L1 protein expression levels in breast cancer tissues with low miRNA-140-3p were significantly higher (P<0.01). Moreover, compared with DOX-sensitive tissues, the levels of PD-L1 protein expression in DOX-resistant tissues were significantly higher (P<0.01). In in vitro and in vivo experiments, the introduction of miRNA-140-3p decreased PD-L1 expression. Mechanically, we found that the MCF7/DOX and HS598T/DOX cells pretreated with miRNA140-3p inhibitor or exosomes containing PD-L1 have higher stemness and lower apoptosis rate, which can be abrogated by co-treating cells with anti-PD-L1 antibody or miRNA-140-3p mimic. Conclusions. MiRNA-140-3p can suppress PD-L1 expression in breast cancer cell-derived exosomes, thereby attenuating the chemoresistance induced by DOX in breast cancer.
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    MiR-101-3p targets KPNA2 to inhibit the progression of lung squamous cell carcinoma cell lines
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Dong, Liangliang; Jiang, Hanliang; Qiu, Ting; Xu, Yiming; Chen, Enguo; Huang, Aihua; Ying, Kejing
    We herein discuss the impacts of miR-101-3p on the tumorigenesis-related cell behaviors in lung squamous cell carcinoma (LUSC) by repressing KPNA2. TCGA database was utilized to measure miR101-3p and KPNA2 levels in LUSC tissues and cells. The interaction of miR-101-3p and KPNA2-3’UTR was determined by dual luciferase assay. Western blot evaluated the protein level of KPNA2. MiR-101-3p was under-expressed in LUSC cells while KPNA2 was overexpressed. Western blot confirmed the impact of KPNA2 expression on cancer cell progression. The negative regulatory impact of miR-101-3p on KPNA2 was also verified. In vitro cell function assays revealed the suppressing effect of high miR-101-3p expression on cell invasion, migration and viability, as well as its promoting effect on apoptosis. Up-regulated miR-101-3p weakened the promoting effect of overexpressed KPNA2 on LUSC malignant progression. To conclude, miR-101-3p repressed viability, invasion, and migration, and facilitated cell apoptosis in LUSC by suppressing KPNA2.
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    Circ_0000284 facilitates the growth, metastasis and glycolysis of intrahepatic cholangiocarcinoma through miR-152-3p-mediated PDK1 expression
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Sun, Jian; Feng, Menglong; Zou, Huilian; Mao, Yanping; Yu, Wei
    Background. Circular RNAs (circRNAs) are key molecules in the regulation of intrahepatic cholangiocarcinoma (ICC) progression. The purpose of this study was to analyze the function and underlying molecular mechanism of circ_0000284 in ICC. Methods. Quantitative real-time PCR was used to analyze the circ_0000284, microRNA (miR)-152-3p and pyruvate dehydrogenase kinase 1 (PDK1) expression. Cell proliferation, apoptosis, invasion and migration were executed by cell counting kit 8 assay, EdU assay, flow cytometry, transwell assay and wound healing assay, respectively. All protein expression levels were examined using western blot analysis. Cell glycolysis was analyzed by detecting glucose consumption, lactate production and ATP/ADP ratios. Target relationship was estimated by dual-luciferase reporter assay. The effect of circ_0000284 on ICC tumor growth in vivo was evaluated by constructing xenograft mice model. Results. We detected high expression of circ_0000284 in ICC tumor tissues and cells. Downregulated circ_0000284 inhibited ICC cell proliferation, invasion, migration, glycolysis, and accelerated apoptosis. MiR-152-3p was sponged by circ_0000284, and its inhibitor revoked the effect of circ_0000284 knockdown on ICC cell progression. PDK1 was a target of miR-152-3p, and its expression was suppressed by circ_0000284 knockdown. PDK1 overexpression reversed the inhibition effect of miR-152-3p on ICC cell growth, metastasis and glycolysis. In animal experiments, circ_0000284 downregulation also inhibited ICC tumor growth. Conclusion. Circ_0000284 promoted the growth, metastasis and glycolysis of ICC by miR-152-3p/PDK1 pathway, showing that circ_0000284 was a potential therapeutic target for ICC.
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    Circ-0000979 promotes the development of gastric carcinoma by sponging miR-136 and modulating SP1 mRNA expression level
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Zhang, Lihua; Xing, Fengjuan; Bao, Lei
    Circular RNAs (circRNAs) are a new class of non-coding RNAs that play pivotal biological roles in several types of cancer cells. However, the role of circ0000979 in gastric cancer (GC) has never been explored. Therefore, the current study aims to examine the functional effects of circ-0000979 in GC development and progression. The expression level of circ-0000979 was validated using qRT-PCR analysis. We found that circ-0000979 is significantly upregulated in GC samples. Using AGS and HGC27 GC cell line, we examined the biological functions and regulatory mechanisms of circ0000979 in GC in vitro and in vivo by knocking down circ-0000979. We found that circ-0000979 is subcellularly localized in the cytoplasm of GC cells. Functionally, silencing circ-0000979 leads to a significant reduction in GC cell proliferation and migration. In vivo assays showed that circ-0000979 knockdown markedly reduced GC tumor growth. CircRNA interactome predicted miR-136 as circ0000979 targeting miRNA, while starbase prediction result showed that miR-136 targeted the 3’UTR region of SP1 mRNA. Taken together, our results demonstrated that circ-0000979, as a carcinogenic circRNA, promotes the progression of GC by regulating the miR-136/SP1 pathway. Circ-0000979 is a potential RNA-based therapeutic target for GC treatment.
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    Hyperin up-regulates miR-7031-5P to promote osteogenic differentiation of MC3T3-E1 cells
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Qian, Dongchen; Chen, Yueyue; Qiu, Xusheng; Zhu, Baohua; Zhang, Lin; Yan, Yifeng; Chen, Yixin
    Objective. To investigate the effects of Hyperin (Hyp) on osteogenic differentiation of MC3T3E1 cells. Methods. Differentially expressed miRNA was screened by miRNA Microarray. miR-7031-5P overexpression and knockdown MC3T3-E1 cell models were constructed by transfecting miR-7031-5P mimics and inhibitor. Alizarin red staining (ARS) assay was used to observe the formation of mineralized nodules in MC3T3-E1 cells. ALP activity was detected by using ALP detection kit. Western blot assay was used to examine the changes in osteogenic differentiation-related proteins. The relationship between miR-7031-5P and Wnt7a was revealed by dual luciferase report experiments. Results. We found that miR-7031-5P was upregulated in MC3T3-E1 cells after Hyp treatment. The results indicated that compared with the untreated group, Hyp promoted the formation of mineralized nodules and the alkaline phosphatase (ALP) activity of MC3T3-E1 cells via overexpressing miR-7031-5P. Besides, elevated miR-7031-5P increased OPN, COL1A1, and Runx2 mRNA expression. More importantly, Wnt7a was identified as the downstream target gene of miR-70315P promoting osteogenic differentiation of MC3T3-E1 cells. Conclusions. Hyp up-regulated miR-7031-5P to promote osteogenic differentiation of MC3T3-E1 cells by targeting Wnt7a