Tumor-suppressive effect of a telomerase-derived peptide by inhibiting hypoxia-induced HIF-1α-VEGF signaling axis

Human cervical cancer is the most common gynecological malignancy. The continuous development of nanotechnology has allowed the wide use of nanomaterials in cancer treatment. Nanoparticles can be used as gene carriers because of their surface effect and small-size effect. MicroRNA-let-7c-5p (miR-let-7c-5p) belongs to the let-7 family. Although it has been reported to exert a tumor suppressive effect in a variety of cancers, the exact role and mechanism of miR-let-7c-5p in the progression of cervical cancer are unclear. In this study, we synthesized flower-shaped SiO2 –PEI nanoparticles with high pDNA/siRNA loading rates. This nanoparticle with miR-let-7c-5p-expressed plasmid could effectively transfer miR-let-7c-5p to human epithelial carcinoma (HeLa) cells. In addition, the combination of nanomaterials and gene therapy could inhibit the development of cancer under the conditions of extremely low cytotoxicity. These findings provided a new anticancer strategy based on F-SiO2 -polyethyleneimine/miR-let-7c-5p (FSP-let-7c-5p)nanoparticles and indicated that miR-let-7c-5p/IGF-1R/PI3K/AKT and -catenin/SLUG could be used as new potential targets for the treatment of cervical cancer.

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LncRNA MONC Suppresses the Malignant Phenotype of Endometrial Cancer Stem Cells by Regulating the MiR-636/GLCE Axis

10.21203/rs.3.rs-40559/v1 ◽

2020 ◽

Author(s):

Yibing Li ◽

Jianing Huo ◽

Junjian He ◽

Haining Ma ◽

Xiaoxin Ma

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Endometrial Cancer ◽

Cancer Stem Cells ◽

Suppressive Effect ◽

Luciferase Assay ◽

Biological Behavior ◽

Mesenchymal Transition ◽

Tumor Suppressive Effect

Abstract Background: Emerging evidence shows that abnormal expression of long non-coding RNA is involved in the occurrence and development of various tumors. LncRNA MONC is abnormally expressed in head and neck squamous cell carcinoma (HNSCC), lung cancer, colorectal cancer, and acute megakaryocytic leukemia, but the biological function and potential regulatory mechanism of MONC in endometrial cancer stem cells (ECSCs) and endometrial cancer cells (ECCs) have not been studied. In this study, we aimed to explore the tumor suppressive effect and mechanism of MONC in regulating ECSCs and ECCs. Methods: The expression of genes was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression of proteins was detected by Western blot. The interplay of LncRNA-miRNA-mRNA was verified using the luciferase assay. The growth rate of ECSC spheroids was detected by sphere formation assay. Cell proliferation was detected by CCK-8 assay. The cell invasion was detected by transwell invasion assay. Cell cycle was detected by Cell cycle analysis.Cell apoptosis was detected by the Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double-staining assay. Animal study was conducted to evaluate the effect of MONC combined with miR-636 on tumor growth in vivo. Results: Low MONC expression in endometrial carcinoma (EC), which directly inhibits the malignant biological behavior of ECSCs and ECCs by directly inhibiting miR-636. Simultaneously, miR-636 may indirectly reduce the expression of MONC. Down-regulation of miR-636 may promote GLCE expression by targeting the 3'-untranslated region (UTR) of the downstream gene GLCE, thereby inhibiting the progression of ECSCs. MONC combined with miR-636 inhibited the Notch signaling pathway and tumor epithelial-to-mesenchymal transition (EMT) process. In addition, we verified the tumor suppressive effect of MONC in nude mice, miR-636 can rescue the tumor suppressive effect of overexpressing MONC, and this effect is more obvious in ECSC. Conclusion: MONC inhibits the malignant phenotypes of ECSCs and ECCs by regulating the miR-636/GLCE axis. The MONC/miR-636/GLCE axis may provide novel treatment avenues for human EC.

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MicroRNA-27a-5p inhibits proliferation, migration and invasion and promotes apoptosis of Wilms tumor cell by targeting PBOV1

10.1101/2021.08.25.457737 ◽

2021 ◽

Author(s):

zhengtuan guo ◽

qiang yv ◽

chunlin miao ◽

wenan ge ◽

peng li

Keyword(s):

Tumor Cells ◽

Wilms Tumor ◽

Suppressive Effect ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Tumor Tissues ◽

And Function ◽

Tumor Suppressive Effect

Wilms tumor is the most common type of renal tumor in children. MicroRNAs (miRNA) are small non-coding RNAs that play crucial regulatory roles in tumorigenesis. We aimed to study the expression profile and function of miR-27a-5p in Wilms tumor. MiR-27a-5p expression was downregulated in human Wilms tumor tissues. Functionally, overexpression of miR-27a-5p promoted cell apoptosis of Wilms tumor cells. Furthermore, upregulated miR-27a-5p delayed xenograft Wilms tumor tumorigenesis in vivo. Bioinformatics analysis predicted miR-27-5p directly targeted to the 3’-untranslated region (UTR) of PBOV1 and luciferase reporter assay confirmed the interaction between miR-27a-5p and PBOV1. The function of PBOV1 in Wilms tumor was evaluated in vitro and knockdown of PBOV1 dampened cell migration. In addition, overexpression of PBOV1 antagonized the tumor-suppressive effect of miR-27a-5p in Wilms tumor cells. Collectively, our findings reveal the regulatory axis of miR-27-5p/PBOV1 in Wilms tumor and miR-27a-5p might serve as a novel therapeutic target in Wilms tumor.

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Propofol exhibits a tumor‑suppressive effect and regulates cell viability, migration and invasion in bladder carcinoma by targeting the microRNA‑10b/HOXD10 signaling pathway

Oncology Letters ◽

10.3892/ol.2019.10968 ◽

2019 ◽

Cited By ~ 1

Author(s):

Zongcai Qi ◽

Lei Yuan ◽

Nenghong Sun

Keyword(s):

Cell Viability ◽

Signaling Pathway ◽

Bladder Carcinoma ◽

Suppressive Effect ◽

Migration And Invasion ◽

Tumor Suppressive Effect

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Cyanidin-3-O-glucoside Inhibits the β-catenin/MGMT Pathway by Upregulating miR-214-5p to Reverse Chemotherapy Resistance in Glioma Cells

10.21203/rs.3.rs-783551/v1 ◽

2021 ◽

Author(s):

Yuan Zhou ◽

Li Chen ◽

Deping Ding ◽

Ziheng Li ◽

Li Cheng ◽

...

Keyword(s):

Cytotoxic Effect ◽

Opposite Effect ◽

Alkylating Agents ◽

Chemotherapy Resistance ◽

Glioma Cells ◽

Suppressive Effect ◽

Signaling Mechanism ◽

Induced Apoptosis ◽

Tumor Suppressive Effect

Abstract Overcoming resistance to alkylating agents has important clinical significance in glioma. Cyanidin-3-O-glucoside (C3G) has a tumor-suppressive effect on tumor cells. However, whether it plays a role in temozolomide resistance in glioma is still unclear. We construct a TMZ-resistant glioma LN-18/TR cells, observe the effect of C3G on TMZ resistance in these cells, and explore the role of miR-214-5p in chemoresistance.Results show that β-catenin and MGMT were significantly upregulated in LN-18/TR cells. C3G upregulated miR-214-5p and enhanced the cytotoxic effect of temozolomide on LN-18/TR cells. C3G downregulated β-catenin and MGMT. The miR-214-5p mimic downregulated β-catenin and MGMT in LN-18/TR cells, whereas the miR-214-5p inhibitor had the opposite effect. The miR-214-5p inhibitor significantly blocked the cyanidin-3-O-glucoside-induced downregulation of β-catenin and MGMT. C3G or the miR-214-5p mimic enhanced temozolomide-induced apoptosis in LN-18/TR cells, whereas the miR-214-5p inhibitor blocked this effect. Further, C3G or miR-214-5p agomir combined with TMZ could significantly inhibit the growth of LN-18/TR tumors. Our research has discovered the potential signaling mechanism associated with C3G-mediated suppression of TMZ resistance in LN-18/TR cells through miR-214-5p, which can facilitate the treatment of MGMT-induced resistance in glioma cells.

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Enhanced Effect of IL-1β-Activated Adipose-Derived MSCs (ADMSCs) on Repair of Intestinal Ischemia-Reperfusion Injury via COX-2-PGE2 Signaling

Stem Cells International ◽

10.1155/2020/2803747 ◽

2020 ◽

Vol 2020 ◽

pp. 1-18

Author(s):

Liu Liu ◽

Yi Ren He ◽

Shao Jun Liu ◽

Lei Hu ◽

Li Chuang Liang ◽

...

Keyword(s):

Therapeutic Effect ◽

Ischemia Reperfusion Injury ◽

Tissue Injury ◽

Ischemia Reperfusion ◽

Suppressive Effect ◽

Signaling Axis ◽

Cox 2 ◽

Underlying Mechanisms ◽

Intestinal Ischemia Reperfusion

Adipose-derived mesenchymal stem cells (ADMSCs) have been used for treating tissue injury, and preactivation enhances their therapeutic effect. This study is aimed at investigating the therapeutic effect of activated ADMSCs by IL-1β on the intestinal ischaemia-reperfusion (IR) injury and exploring potential mechanisms. ADMSCs were pretreated with IL-1β in vitro, and activation of ADMSCs was assessed by α-SMA and COX-2 expressions and secretary function. Activated ADMSCs was transplanted into IR-injured intestine in a mouse model, and therapeutic effect was evaluated. In addition, to explore underlying mechanisms, COX-2 expression was silenced to investigate its role in activated ADMSCs for treatment of intestinal IR injury. When ADMSCs were pretreated with 50 ng/ml IL-1β for 24 hr, expressions of α-SMA and COX-2 were significantly upregulated, and secretions of PGE2, SDF-1, and VEGF were increased. When COX-2 was silenced, the effect of IL-1β treatment was abolished. Activated ADMSCs with IL-1β significantly suppressed inflammation and apoptosis and enhanced healing of intestinal IR injury in mice, and these effects were impaired by COX-2 silencing. The results of RNA sequencing suggested that compared with the IR injury group activated ADMSCs induced alterations in mRNA expression and suppressed the activation of the NF-κB-P65, MAPK-ERK1/2, and PI3K-AKT pathways induced by intestinal IR injury, whereas silencing COX-2 impaired the suppressive effect of activated ADMSCs on these pathway activations induced by IR injury. These data suggested that IL-1β pretreatment enhanced the therapeutic effect of ADMSCs on intestinal IR injury repairing via activating ADMSC COX-2-PGE2 signaling axis and via suppressing the NF-κB-P65, MAPK-ERK1/2, and PI3K-AKT pathways in the intestinal IR-injured tissue.

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