Delivery of MicroRNA-let-7c-5p by Biodegradable Silica Nanoparticles Suppresses Human Cervical Carcinoma Cell Proliferation and Migration

2020 ◽  
Vol 16 (11) ◽  
pp. 1600-1611
Author(s):  
L.Y. Shao ◽  
R.R. Wang ◽  
Y.S. Sun ◽  
Z. Yue ◽  
H. Sun ◽  
...  

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.

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Jie Zeng ◽  
Si-Li He ◽  
Li-Jie Li ◽  
Chen Wang

Abstract Background HPV16 is the predominant cancer-causing strain that is responsible for over 50% of all cervical cancers. In this study, we aim to investigate the therapeutic effect of heat shock protein 90 (Hsp90) knockdown on HPV16+ cervical cancer progression and the underlying mechanism. Methods The transcript and protein expression of Hsp90 in normal cervical and HPV16+ cervical cancer tissues and cell lines were detected by qRT-PCR, immunohistochemistry staining and Western blot. Hsp90 knockdown clones were established using HPV16+ cervical cancer cell line Caski and SiHa cells. The effect of Hsp90 knockdown on HER2/PI3K/AKT pathway and PD-L1 expression was characterized using qRT-PCR and Western blot analysis. Cell proliferation and migration were determined using MTT and transwell assays. Using mouse xenograft tumor model, the impact of Hsp90 knockdown and PD-L1 overexpression on tumor progression was evaluated. Results Hsp90 expression was up-regulated in HPV16+ cervical cancer tissues and cells. Knockdown of Hsp90 inhibited proliferation and migration of Caski and SiHa cells. PD-L1 expression in cervical cancer tissues was positively correlated with Hsp90 expression, and Hsp90 regulated PD-L1 expression via HER2/PI3K/AKT signaling pathway. The results of mouse xenograft tumor model demonstrated Hsp90 knockdown suppressed tumor formation and overexpression of PD-L1 simultaneously eliminated the cancer-suppressive effect of Hsp90 knockdown. Conclusion In this study, we demonstrated a promising tumor-suppressive effect of Hsp90 knockdown in HPV16+ cervical cancers, and investigated the underlying molecular pathway. Our results suggested that Hsp90 knockdown holds great therapeutic potential in treating HPV16+ cervical cancers.


RSC Advances ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 5230-5230
Author(s):  
Laura Fisher

Retraction of ‘RNA-sequencing identified miR-3681 as a negative regulator in the proliferation and migration of cervical cancer cells via the posttranscriptional suppression of HGFR’ by Fan Shi et al., RSC Adv., 2019, 9, 22376–22383, DOI: 10.1039/C9RA01785B.


RSC Advances ◽  
2019 ◽  
Vol 9 (39) ◽  
pp. 22376-22383 ◽  
Author(s):  
Fan Shi ◽  
Yingbing Zhang ◽  
Juan Wang ◽  
Jin Su ◽  
Zi Liu ◽  
...  

In this study, RNA-sequencing was used to investigate the differentially expressed miRNAs between cervical cancer tissues and matched adjacent non-tumor tissues.


2014 ◽  
Vol 37 (3) ◽  
pp. 131 ◽  
Author(s):  
Yi Sun ◽  
Bo Zhang ◽  
Jiajing Cheng ◽  
Yi Wu ◽  
Fing Xing ◽  
...  

Purpose: This study aimed to investigate the role of small non-coding RNA-222 (microRNA-222; miR-222) in the development of cervical cancer (CC). Methods: Normal and CC specimens were obtained from 18 patients. HeLa and SiHa cells were grown in Dulbecco’s modified Eagle’s medium. RT–PCR, Western blot, migration assay, flow cytometry and immunofluorescence microscopy were used for analyses. Results: When compared with normal cervical tissues, miR-222 was upregulated in human CC, and the extent of up-regulation was associated with the extent and depth of CC invasion. Expression of miR-222 was inversely related to the expression of phosphatase and tensin homolog (PTEN) and p27. The reduced the expression of PTEN and p27 by miR-222 in HeLa cells and SiHa cells was associated with increased proliferation and migration of CC cells. The expression of proteins (E-cadherin and paxillin) related to the proliferation and migration was also elevated. Conclusion: MiR-222 plays an important role in the tumorigenesis of CC, possibly by specifically down-regulating p27Kip1 and PTEN. Our findings suggest that miR-222 may serve as a new therapeutic target in CC.


2019 ◽  
Vol 20 (3) ◽  
pp. 545 ◽  
Author(s):  
Sergio Córdova-Rivas ◽  
Ixamail Fraire-Soto ◽  
Andrea Mercado-Casas Torres ◽  
Luis Servín-González ◽  
Angelica Granados-López ◽  
...  

The micro RNA (miR)-34 family is composed of 5p and 3p strands of miR-34a, miR-34b, and miR-34c. The 5p strand’s expression and function is studied in cervical cancer. The 3p strand’s function and regulation remain to be elucidated. To study the function of the passenger strands of miR-34 family members, we overexpressed 5p and 3p strands using a synthetic miRNA in cervical cell lines. Cell proliferation was evaluated using crystal violet. Migration and invasion were tested using transwell assays, Western blot, and zymography. Possible specific targets and cell signaling were investigated for each strand. We found that miR-34a-5p inhibited proliferation, migration, and cell invasion accompanied by matrix metalloproteinase 9 (MMP9) activity and microtubule-associated protein 2 (MAP2) protein reduction. We also found that miR-34b-5p and miR-34c-5p inhibit proliferation and migration, but not invasion. In contrast, miR-34c-5p inhibits MMP9 activity and MAP2 protein, while miR-34b-5p has no effect on these genes. Furthermore, miR-34a-3p and miR-34b-3p inhibit proliferation and migration, but not invasion, despite the later reducing MMP2 activity, while miR-34c-3p inhibit proliferation, migration, and cell invasion accompanied by MMP9 activity and MAP2 protein inhibition. The difference in cellular processes, MMP2 and MMP9 activity, and MAP2 protein inhibition by miR-34 family members suggests the participation of other regulated genes. This study provides insights into the roles of passenger strands (strand*) of the miR-34 family in cervical cancer.


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