The role of calgranulin B gene on the biological behavior of squamous cervical cancer in vitro and in vivo

Abstract Background There is growing evidence discussing the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). We performed this study to explore the impact of exosomal lncRNA urothelial cancer-associated 1 (UCA1) in CC stem cells by sponging microRNA-122-5p (miR-122-5p) and regulating SOX2 expression. Methods CC stem cells (CD133+CaSki) and exosomes were extracted and identified. The synthesized UCA1- and miR-122-5p-related sequences were transfected into CaSki cells, CaSki cells-derived exosomes were extracted and then co-cultured with CD133+CaSki cells. The functional roles of UCA1 and miR-122-5p in self-renewal and differentiation ability of CC stem cells were determined using ectopic expression, knockdown/depletion and reporter assay experiments. An in vivo experiment was performed to verify the in vitro results. Results Up-regulated UCA1 and SOX2 and down-regulated miR-122-5p were found in CaSki-Exo. Exosomes promoted invasion, migration, proliferation and restrained apoptosis of CD133+CaSki cells. Silencing UCA1 or up-regulating miR-122-5p degraded SOX2 expression, and reduced invasion, migration and proliferation of CD133+CaSki cells while advanced apoptosis and suppressed the tumor volume and weight in nude mice. Conclusion Our study provides evidence that CaSki-Exo can promote the self-renewal and differentiation ability of CC stem cells while silencing UCA1 or up-regulating miR-122-5p restrains self-renewal and differentiation of CC stem cells.

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Histone Deacetylase Inhibitors as Therapeutic Interventions on Cervical Cancer Induced by Human Papillomavirus

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.592868 ◽

2021 ◽

Vol 8 ◽

Author(s):

Natália Lourenço de Freitas ◽

Maria Gabriela Deberaldini ◽

Diana Gomes ◽

Aline Renata Pavan ◽

Ângela Sousa ◽

...

Keyword(s):

Cervical Cancer ◽

Histone Deacetylases ◽

Histone Deacetylase Inhibitors ◽

Hdac Inhibitors ◽

Human Papillomaviruses ◽

Therapeutic Interventions ◽

Cellular Targets

The role of epigenetic modifications on the carcinogenesis process has received a lot of attention in the last years. Among those, histone acetylation is a process regulated by histone deacetylases (HDAC) and histone acetyltransferases (HAT), and it plays an important role in epigenetic regulation, allowing the control of the gene expression. HDAC inhibitors (HDACi) induce cancer cell cycle arrest, differentiation, and cell death and reduce angiogenesis and other cellular events. Human papillomaviruses (HPVs) are small, non-enveloped double-stranded DNA viruses. They are major human carcinogens, being intricately linked to the development of cancer in 4.5% of the patients diagnosed with cancer worldwide. Long-term infection of high-risk (HR) HPV types, mainly HPV16 and HPV18, is one of the major risk factors responsible for promoting cervical cancer development. In vitro and in vivo assays have demonstrated that HDACi could be a promising therapy to HPV-related cervical cancer. Regardless of some controversial studies, the therapy with HDACi could target several cellular targets which HR-HPV oncoproteins could be able to deregulate. This review article describes the role of HDACi as a possible intervention in cervical cancer treatment induced by HPV, highlighting the main advances reached in the last years and providing insights for further investigations regarding those agents against cervical cancer.

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CDK12 Promotes Cervical Cancer Progression through Enhancing Macrophage Infiltration

Journal of Immunology Research ◽

10.1155/2021/6645885 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Bikang Yang ◽

Jing Chen ◽

Yincheng Teng

Keyword(s):

Cervical Cancer ◽

Cancer Progression ◽

Therapeutic Target ◽

Macrophage Infiltration ◽

Patient Death ◽

Mrna And Protein Expression ◽

Underlying Mechanisms

Cervical cancer (CC) is a commonly diagnosed and primary consideration of cancer patient death in female reproductive system malignancy. Cyclin-dependent kinase 12 (CDK12), as a transcription-associated CDK, plays important roles in tumor-promoting behaviors, whereas the underlying mechanisms of CDK12 in CC progression are still obscure. In this report, we investigated the role of CDK12 in cervical cancer. The current study identified CDK12 mRNA and protein expression remarkably upregulated in CC patients. Upregulated CDK12 was closely associated with CC progression and poor prognosis. In vitro and in vivo functional experiments showed that knockdown of CDK12 inhibited cancer cell proliferation and colony formation and promoted apoptosis. Further investigations demonstrated that CDK12 regulated the immune microenvironment to facilitate the progression of CC cells by promoting macrophage infiltration. Meanwhile, we first demonstrated that nuclear import of CDK12 is mediated by TNPO1 and might be a new therapeutic target in oncology. Collectively, this study pointed out the potential of CDK12 to serve as a novel therapeutic target in restricting CC proliferation and cell cycle process through promoting macrophage infiltration.

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Role of chemokine receptors in thyroid cancer and immunotherapy

Endocrine Related Cancer ◽

10.1530/erc-19-0163 ◽

2019 ◽

Vol 26 (8) ◽

pp. R465-R478 ◽

Cited By ~ 12

Author(s):

Francesca Coperchini ◽

Laura Croce ◽

Michele Marinò ◽

Luca Chiovato ◽

Mario Rotondi

Keyword(s):

Thyroid Cancer ◽

Tumor Microenvironment ◽

Chemokine Receptors ◽

Current Knowledge ◽

Biological Effects ◽

Biological Behavior ◽

Thyroid Cells

Inflammation is currently regarded as an essential component of malignancies. It is now known that the tumor microenvironment may profoundly influence the biological behavior of cancer cells and ultimately the patient’s outcome. Chemokine and their receptor play a major role in determining the immune phenotype of the cells infiltrating the thyroid tumor microenvironment. Experimental evidence shows that both normal and cancer thyroid cells express specific chemokine receptors. The expression of at least some of these receptors exerts several biological effects, which influence the course of the disease. The present review article will take into account the role of the most studied chemokine receptors (CXCR1, CXCR2, CXCR3, CXCR4, CXCR7, DARC, CCR3, CCR6 and CCR7) in the context of thyroid cancer. This review will focus on current knowledge provided by in vitro and in vivo studies specifically performed on thyroid cancer including (i) expression of chemokine receptors in normal and cancer thyroid cells; (ii) role of chemokine receptors in affecting the biological behavior of thyroid tumors including the metastatic process; (iii) current knowledge about immunotherapies through targeting of chemokine receptors in thyroid cancer.

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Study on Chlorogenic Acid Inhibiting the Proliferation and Invasion of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis Model

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2797 ◽

2021 ◽

Vol 11 (11) ◽

pp. 2192-2196

Author(s):

Mingjuan Zhang ◽

Huaming Deng ◽

Xiajun Yi ◽

Siying Xie ◽

Qingying Zhan

Keyword(s):

Rheumatoid Arthritis ◽

Chlorogenic Acid ◽

Cell Invasion ◽

Detection System ◽

Inhibitory Effect ◽

Biological Behavior ◽

Proliferation And Invasion

This paper explored Chlorogenic acid regulating the biological behavior of RA FLSs and studied the functional role of microRNAs in it. In vivo experiment: Female DBA/1 J mice were used for model establishment and grouping. HE staining was employed. The damage of ankle cartilage was analyzed in each group of mice. The levels of serum cytokines TNF-α and IL-β were measured by ELISA. In vitro experiment: The cells were counterstained with Hoechst 33342, Transwell was used to detect cell invasion. Western blotting was used to detect the expression of Akt protein. The Akt expression plasmid and miR-23b mimic were co-transfected into RA FLSs, and the luciferase activity was measured using a dual-luciferase detection system. In vivo experiments found that Chlorogenic acid can significantly reduce arthritis index and inhibit TNF-α and IL-β levels. In vitro experiments found that TNF-α-induced proliferation of RA FLSs was significantly inhibited by Chlorogenic acid. Transwell invasion test showed that TNF-α-induced cell invasion was attenuated at the presence of Chlorogenic acid, which significantly inhibited Akt protein expression and phosphorylation. The expression of miR-23b in Chlorogenic acid-treated RA-FLSs increased, and silencing miR-23b enhanced the inhibitory effect of RA FLSs on Chlorogenic acid induction. Chlorogenic acid has potential anti-rheumatoid arthritis activity. Its inhibition of RA FLSs proliferation and invasion is related to the induction of miR-23b and the down-regulation of Akt expression.

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A novel protein encoded by circMAPK1 inhibits progression of gastric cancer by suppressing activation of MAPK signaling

Molecular Cancer ◽

10.1186/s12943-021-01358-y ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Tianlu Jiang ◽

Yiwen Xia ◽

Jialun Lv ◽

Bowen Li ◽

Ying Li ◽

...

Keyword(s):

Mass Spectrometry ◽

Gastric Cancer ◽

Cancer Cells ◽

Mapk Pathway ◽

Biological Behavior ◽

Gastric Cancer Cells ◽

Novel Protein

Abstract Background A novel type of noncoding RNA, circRNA has been reported to participate in the occurrence and development of diseases through many mechanisms. The MAPK pathway is a common signal transduction pathway involved in cell proliferation, inflammation and apoptosis and plays a particularly important role in cancers. However, the role of circRNAs related to the MAPK pathway in gastric cancer has not been explored. Methods A bioinformatics analysis was performed to profile and identify the circRNAs involved in the MAPK pathway in gastric cancer. The tumor-suppressive role of circMAPK1 was confirmed both in vitro and in vivo. Mass spectrometry, Western blot and immunofluorescence staining assays were used to validate the existence and expression of MAPK1–109aa. The molecular mechanism of circMAPK1 was investigated by mass spectrometry and immunoprecipitation analyses. Results In this study, we identified that circMAPK1 (hsa_circ_0004872) was downregulated in gastric cancer tissues compared with adjacent normal tissues. Importantly, lower circMAPK1 expression predicted poor survival in GC patients. CircMAPK1 inhibited the proliferation and invasion of gastric cancer cells in vitro and in vivo. Next, we found that circMAPK1 encoded a novel protein with 109 amino acids in length. Through a series of functional experiments, we confirmed that circMAPK1 exerted a tumor-suppressing effect via the encoded protein MAPK1–109aa. Mechanistically, the tumor suppressor MAPK1–109aa inhibited the phosphorylation of MAPK1 by competitively binding to MEK1, thereby suppressing the activation of MAPK1 and its downstream factors in MAPK pathway. Conclusions Our study revealed that circMAPK1 inhibits the malignant biological behavior of gastric cancer cells through its encoded protein MAPK1–109aa. More importantly, circMAPK1 is a favorable predictor for gastric cancer patients and may provide a new therapeutic target in the treatment of gastric cancer.

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RPL22 Overexpression Promotes Psoriasis-Like Lesion by Inducing Keratinocytes Abnormal Biological Behavior

Frontiers in Immunology ◽

10.3389/fimmu.2021.699900 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jinrong Zeng ◽

Yue Zhang ◽

Hanyi Zhang ◽

Yuezhong Zhang ◽

Lihua Gao ◽

...

Keyword(s):

Skin Lesions ◽

Biological Behavior ◽

Clinical Samples ◽

Keratinocyte Proliferation ◽

Histone H3k27 ◽

Accelerated Proliferation ◽

Apoptosis Process

BackgroundKeratinocytes of psoriasis have anti-apoptotic properties including delayed apoptosis process, accelerated proliferation metabolism and postponed differentiation process. However, the specific mechanism leading to the abnormal biological behavior of keratinocytes remains unclear.ObjectivesWe investigated the role of increased RPL22 expression in regulating the abnormal biological behavior of keratinocytes and the mechanism of regulation of RPL22 expression in skin lesions of psoriatic patients.MethodsWe examined clinical samples and utilized cytokine-induced cell and IMQ-treated mouse models. We determined the expression and functions of RPL22 in vitro and in vivo.ResultsWe showed that RPL22 expression was significantly increased in the skin lesions of psoriasis patients and IMQ-treated psoriatic-like mice. Such increased expression is attributed to hyperacetylation of histone H3K27 in the promoter region of RPL22. Interestingly, overexpression of RPL22 enhanced keratinocyte proliferation by increasing cyclinD1 expression and accelerated CD4+T cells recruitment via upregulating CXCL10 expression. Finally, we demonstrated that RPL22 overexpression promoted psoriasiform phenotypes in IMQ-induced mouse skins.ConclusionsThese findings suggested that RPL22 regulates keratinocytes abnormal biological behavior and contributes to the development of psoriatic phenotypes. Thus, RPL22 might be a novel potential molecular target for treatment of psoriasis.

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AGER promotes proliferation and migration in cervical cancer

Bioscience Reports ◽

10.1042/bsr20171329 ◽

2018 ◽

Vol 38 (1) ◽

Cited By ~ 4

Author(s):

Xuejie Zhu ◽

Lulu Zhou ◽

Ruyi Li ◽

Qi Shen ◽

Huihui Cheng ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Tumor Promoter ◽

Biological Behavior ◽

Squamous Cervical Cancer ◽

Glycation End Products ◽

Squamous Cancer ◽

And Migration ◽

Cervical Squamous Cancer

The receptor for advanced glycation end products (AGER) is an oncogenic transmembranous receptor up-regulated in various human cancers. We have previously reported that AGER was overexpressed in squamous cervical cancer. However, mechanisms of AGER involved in the progression of cervical cancer are unknown. In the present study, we investigated the effects of AGER on biological behavior, including proliferation, apoptosis, and migration using multiple biological approaches. AGER protein primarily localized in the cytoplasm and cytomembrane of cervical squamous cancer cells. Blockage of AGER with multiple siRNAs suppressed proliferation, stimulated apoptosis, inhibited migration of cervical squamous cancer cells. Conversely, overexpression of AGER increased cell proliferation, migration, and inhibited cell apoptosis. These results indicate that AGER promotes proliferation, migration, and inhibits apoptosis of squamous cervical cancer and might function as a tumor promoter in cervical cancer. Our study provides novel evidence for a potential role of AGER in bridging human papillomavirus (HPV)-induced inflammation and cervical cancer.

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ER-α36 Promotes the Malignant Progression of Cervical Cancer Mediated by Estrogen via HMGA2

Frontiers in Oncology ◽

10.3389/fonc.2021.712849 ◽

2021 ◽

Vol 11 ◽

Author(s):

Chunyan Wang ◽

Tianli Zhang ◽

Kun Wang ◽

Shuo Zhang ◽

Qing Sun ◽

...

Keyword(s):

Cervical Cancer ◽

Estrogen Receptor ◽

Cancer Cells ◽

Poor Prognosis ◽

High Mobility ◽

High Expression ◽

Cervical Cancer Cells

ObjectivesEstrogen is proven to promote the malignant behaviors of many cancers via its receptors. Estrogen receptor alfa 36 (ER-α36) is a newly identified isoform of estrogen receptor alfa (ER-α), the role of ER-α36 in regulating the effects of estrogen and its potential impact on human cervical cancer is poorly understood.MethodsImmunohistochemistry staining was used to evaluate the expression of ER-α36, estrogen receptor alfa 66 (ER-α66) and their prognostic values in cervical cancer. The effects of ER-α36 and ER-α66 on the proliferation and metastasis of cervical cancer were measured in vitro. A xenograft tumor assay was used to study the tumorigenesis role of ER-α36 in vivo. Furthermore, the functional gene at the downstream of ER-α36 was obtained via next-generation sequencing, and the biological functions of high mobility group A2 (HMGA2) in cervical cancer cells were investigated in vitro.ResultsER-α36 was over-expressed in cervical cancer tissues and elevated ER-α36 expression was associated with poor prognosis in cervical cancer patients. High expression of ER-α36 promoted the proliferation, invasion and metastasis of cervical cancer cells mediated by estrogen, while silencing ER-α36 had the opposite effects. Further research showed that HMGA2 was a downstream target of ER-α36 in cervical cancer cells. The oncogenic effect of ER-α36 was attenuated after HMGA2 knockdown.ConclusionsHigh expression of ER-α36 was correlated with a poor prognosis in cervical cancer by regulating HMGA2. ER-α36 could be a prognostic biomarker and a target for cervical cancer treatment.

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