A number of studies have demonstrated that circular RNA (circRNA) plays a critical role in tumorigenesis and tumor progression. However, the biological effects of most circRNAs on cervical cancer ...remain unclear. Hsa_circ_0021087 (thereafter named circLMO1) is a circRNA generated from the circularization of exon 2 and exon 3 of LIM Domain Only 1 (
) and first identified as a tumor suppressor in gastric cancer. We aimed to identify the role of circLMO1 in cervical cancer progression.
CircLMO1 was verified through qPCR and Sanger sequencing. The biological role of circLMO1 in regulating cervical cancer growth and metastasis was investigated both
and in the nude mouse xenograft tumor model. The dual luciferase reporter assay and rescue experiment were conducted to evaluate the interactions among circLMO1, microRNA (miR)-4291, and acyl-CoA synthetase long chain family member 4 (ACSL4). The role of circLMO1 in regulating ferroptosis was assessed by analyzing lipid reactive oxygen species (ROS), and malonyl dialdehyde (MDA), and glutathione (GSH) content.
The level of circLMO1 was down-regulated in cervical cancer tissues and was associated with the International Federation of Gynecology and Obstetrics (FIGO) staging. Functionally, circLMO1 overexpression inhibited cervical cancer growth and metastasis both
and
, whereas circLMO1 depletion promoted cervical cancer cell proliferation and invasion. Mechanistically, circLMO1 acted as a competing endogenous RNA (ceRNA) by sponging miR-4192 to repress target gene
. CircLMO1 promoted cervical cancer cell ferroptosis through up-regulating ACSL4 expression. Overexpression of miR-4291 or knockdown of ACSL4 reversed the effect of circLMO1 on facilitating ferroptosis and repressing cervical cancer cell proliferation and invasion.
CircLMO1 acted as a tumor suppressor of cervical cancer by regulating miR-4291/
-mediated ferroptosis, and could be a promising biomarker for the clinical management of cervical cancer.
Statistics show that the prognosis of cervical cancer (CC) is poor, and the death rate of CC in advanced stage has been rising in recent years. Increasing evidence has demonstrated that circular RNAs ...(circRNAs) serve as promising biomarkers in human cancers, including CC. The present study planned to find out the circRNA involved in CC and to explore its regulatory mechanism in CC. We discovered the new circRNA, circ-0033550, upregulated in CC. Its associated gene was AKT (also known as protein kinase B) serine/threonine kinase 1 (AKT1), so we renamed circ-0033550 as circ-AKT1. We confirmed the high expression of circ-AKT1 in CC samples and cell lines, as well as the circle structure of circ-AKT1. Functionally, gain- and loss-of-function experiments indicated that circ-AKT1 and AKT1 promoted CC cell proliferation and invasion. Moreover, circ-AKT1 and AKT1 were induced by transforming growth factor beta (TGF-β) and facilitated EMT (epithelial-mesenchymal transition) in CC. Mechanically, we illustrated that circ-AKT1 upregulated AKT1 by sponging miR-942-5p. Rescue assays confirmed the role of the circ-AKT1/miR-942-5p/AKT1 axis in CC progression. In vivo assays validated that circ-AKT1 promoted tumor growth in CC. Overall, circRNA-AKT1 sequestered miR-942-5p to upregulate AKT1 and promote CC progression, which may offer a new molecular target for the treatment improvement of CC.
Cervical cancer is acknowledged as the most prevalent gynecological tumor and a severe public issue that threatens female health, resulting from its high incidence and fatality rate. Surging evidence ...have shown that circular RNAs (circRNAs) play significant roles in the initiation and progression of various malignancies. Although circAMOTL1 has been testified to execute oncogenic properties in breast cancer and prostate cancer, literature on its function and regulatory mechanism in cervical cancer development is still scanty. Using a bioinformatics analysis, we found circ_0004214 was a circular form of AMOTL1. Through qRT-PCR analysis, circAMOTL1 and its host gene AMOTL1 were both upregulated in cervical cancer tissues and closely correlated with poor prognosis of cervical cancer. Gain- or loss-of-function assays and in vivo experiments demonstrated that AMOTL1 promoted cervical cancer cell growth both in vitro and in vivo. Mechanically, circAMOTL1 served as a competing endogenous RNA (ceRNA) to prompt the expression of AMOTL1 through sponging miR-485-5p. Rescue assays revealed that miR-485-5p/AMOTL1 axis was involved in circ_AMOTL1-mediated cervical cancer progression. Our findings provide a better understanding of the molecular mechanism underlying circAMOTL1 in cervical cancer and indicated circAMOTL1/miR-485-5p/AMOTL1 as a promising novel therapeutic strategy for the treatment of this disease.
We are committed to investigate miR-218-5 effects on the progression of cervical cancer (CC) cell and find out the molecular mechanism.
GSE9750 was obtained from GEO database and R Limma package was ...applied to filter out dysregulated genes. The pathways were enriched by GSEA software, ClusterProfiler and enrichplot packages to predict the function of DEGs. The binding sites of
were detected by miRanda and TargetScan. The miR2Disease database was used to find miRNAs related with CC. The expression of miR-218-5p and
were quantified by qRT-PCR and that of LYN protein was measured by western blot. The targeted relationships between miR-218-5p and
were verified by dual-luciferase reporter assay. Colony formation assays, wound healing, transwell invasion assay and flow cytometer analysis were performed to investigate the roles that miR-218-5p and
played in migration, invasion and death of cervical carcinoma. Xenografts established in nude mice were used to assess tumor growth in vivo.
The highly expressed mRNA
was selected by microarray analysis in GSE9750. NF-κB signaling pathway was enriched base on GSEA results. The expression of miR-218-5p was lower but
was higher in CC primary tumors compared with normal control. In addition, miR-218-5p could regulate the expression of
in HeLa cells negatively. Overexpression of
could promote cell migration and invasion, but inhibit cell death in vitro, and also promote tumor formation in vivo via activating NF-κB signaling pathway which could be reversed by miR-218-5p.
MiR-218-5p suppressed the progression of CC via
/NF-κB signaling pathway.
Wound management remains a worldwide challenge. It is undeniable that patients with problems such as difficulties in wound healing, metabolic disorder of the wound microenvironment and even severely ...infected wounds
always suffer great pain that affected their quality of lives. The selection of appropriate wound dressings is vital for the healing process. With the advances of technology, hydrogels dressings have been showing great potentials for the treatment of both acute wounds (e.g., burn injuries, hemorrhage, rupturing of internal organs/aorta) and chronic wounds such as diabetic foot and pressure ulcer. Particularly, in the past decade, polysaccharide-based hydrogels which are made up with abundant and reproducible natural materials that are biocompatible and biodegradable present unique features and huge flexibilities for modifications as wound dressings and are widely applicable in clinical practices. They share not only common characteristics of hydrogels such as excellent tissue adhesion, swelling, water absorption,
, but also other properties (
anti-inflammatory, bactericidal and immune regulation), to accelerate wound re-epithelialization, mimic skin structure and induce skin regeneration. Herein, in this review, we highlighted the importance of tailoring the physicochemical performance and biological functions of polysaccharide-based hydrogel wound dressings. We also summarized and discussed their clinical states of, aiming to provide valuable hints and references for the future development of more intelligent and multifunctional wound dressings of polysaccharide hydrogels.
Trim-Away is a recent technique to rapidly deplete a protein from any cell type. Guided by antibodies, TRIM21 selects proteins for destruction. However, the applicability of this method in model ...organisms has not been investigated. Here, we show that Trim-Away can degrade proteins in zebrafish embryos. Trim-Away depletes proteins faster than morpholinos, which enables analysis of protein function during early embryogenesis. Furthermore, Trim-Away can be applied to evaluate the role of maternally contributed proteins in zebrafish embryos. Our findings indicate that Trim-Away is a powerful tool to perform functional analysis of proteins during zebrafish development.
Emerging evidence indicates that microRNAs play critical roles in carcinogenesis and cancer progression. In this study, miR-133a was found to be significantly downregulated in colon tumor tissues. We ...aimed to determine its biological function, molecular mechanisms, and direct target genes in colorectal cancer. From these results, we found that miR-133a was significantly downregulated in primary tumor tissues and colon cancer cell lines. Ectopic expression of miR-133a in colon cancer cell lines significantly suppressed cell growth, as evidenced by cell viability and colony formation assays, as well as reduced xenograft tumor growth in nude mice. However, the effect of miR-133a was abolished by the overexpression of eIF4A1. Moreover, miR-133a inhibited cellular migration and invasiveness. A luciferase activity assay revealed oncogene eukaryotic translation initiation factor 4A1 as a direct target gene of miR-133a, whose expression was inversely correlated with that of miR-133a. Our results demonstrate that miR-133a plays a pivotal role in colorectal cancer by inhibiting cell proliferation, invasion, and migration by targeting oncogenic eukaryotic translation initiation factor 4A1, which acts as a tumor suppressor and may provide a new potential therapeutic target in colorectal cancer.
Human papillomavirus (HPV)-mediated cervical carcinogenesis is a multistep progressing from persistent infection, precancerous lesion to cervical cancer (CCa). Although molecular alterations driven ...by viral oncoproteins are necessary in cervical carcinogenesis, the key regulators behind the multistep process remain not well understood. It is pivotal to identify the key genes involved in the process for early diagnosis and treatment of this disease. Here we analyzed the mRNA expression profiles in cervical samples including normal, cervical intraepithelial neoplasia (CIN), and CCa. A co-expression network was constructed using weighted gene co-expression network analysis (WGCNA) to reveal the crucial modules in the dynamic process from HPV infection to CCa development. Furthermore, the differentially expressed genes (DEGs) that could distinguish all stages of progression of CCa were screened. The key genes involved in HPV-CCa were identified. It was found that the genes involved in DNA replication/repair and cell cycle were upregulated in CIN compared with normal control, and sustained in CCa, accompanied by substantial metabolic shifts. We found that upregulated fibronectin type III domain-containing 3B (FNDC3B) and downregulated bisphosphoglycerate mutase (BPGM) could differentiate all stages of CCa progression. In patients with CCa, a higher expression of FNDC3B or lower expression of BPGM was closely correlated with a shorter overall survival (OS) and disease-free survival (DFS). A receiver operating characteristic (ROC) analysis of CIN and CCa showed that FNDC3B had the highest sensitivity and specificity for predicting CCa development. Taken together, the current data showed that FNDC3B and BPGM were key genes involved in HPV-mediated transformation from normal epithelium to precancerous lesions and CCa.
Immunotherapy has emerged as a promising strategy for cancer treatment, in which durable immune responses were generated in patients with malignant tumors. In the past decade, biomaterials have ...played vital roles as smart drug delivery systems for cancer immunotherapy to achieve both enhanced therapeutic benefits and reduced side effects. Hydrogels as one of the most biocompatible and versatile biomaterials have been widely applied in localized drug delivery systems due to their unique properties, such as loadable, implantable, injectable, degradable and stimulus responsible. Herein, we have briefly summarized the recent advances on hydrogel-by-design delivery systems including the design of hydrogels and their applications for delivering of immunomodulatory molecules (e.g., cytokine, adjuvant, checkpoint inhibitor, antigen), immune cells and environmental regulatory substances in cancer immunotherapy. We have also discussed the challenges and future perspectives of hydrogels in the development of cancer immunotherapy for precision medicine at the end.
Melanoma, the most aggressive skin cancer that originated from genetic mutations in the melanocytes, is still a troublesome medical problem under the current therapeutic approaches, which include ...surgical resection, chemotherapy, photodynamic therapy, immunotherapy, biochemotherapy and targeted therapy. Nanotechnology has significantly contributed to the development of cancer treatment in the past few years, among which extracellular vesicles (EVs) are nanosized lipid bilayer vesicles secreted from almost all cells that play essential roles in many physiological and pathological processes. In terms of melanoma therapy, the unique physicochemical properties of EVs make them promising nanocarriers for drug transportation compared to other synthetic nanocarriers. Moreover, EVs can be further engineered to maximize their drug delivery potential. Herein, in this minireview, we gave a brief overview of EV-based drug delivery strategies for melanoma therapy, in which different therapeutics delivered
via
EVs were summarized. We also highlighted the current progress of the EV-based delivery platform for melanoma therapy in clinical trials. The obstacles to applying exosomes in clinical practice toward further translation of EVs melanoma therapy were also discussed at the end. In summary, EVs offer promising prospects for melanoma therapy, whilst the ways for unlocking EVs’ full potential in melanoma therapies should be further investigated by solving relevant issues which hamper EVs-based melanoma therapy translation in the future.
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