Hyperglycemia and hyperinsulinemia stimulate cervical cancer cell proliferation in vitro and in vivo study

Abstract Background: Diabetes mellitus and malignant tumor are the second and third causes of women death in Mexico. Hyperglycemia, insulin and insulin-like growth factor 1 are the main risk factors involved in cancer development in patient with diabetes. The aim of this study was to evaluate the effect of hyperglycemia and hyperinsulinemia over cell proliferation and tumor growth in cervical cancer. Methods: Cell proliferation, apoptosis and cell cycle of cervical cancer cell lines (HeLa, SiHa and CaSki) in presence of hyperglycemia and/or insulin were evaluated. Xenograft model for cervical cancer was done in diabetic female nu/nu mice; biochemical parameters, body weight, tumoral volume and cell doubling time were evaluated. Results: Hyperglycemia and hyperinsulinemia significantly increase cell proliferation and decreases apoptosis with no change in cell cycle. Insulin treatment increase tumor volume and diminish cell doubling time, this group also developed hyperinsulinemia and in Langerhans pancreatic islet hypertrophy; whereas, hyperglycemic groups show the same effects but in lesser degree than the insulin treated group. Conclusion: Glucose and insulin stimulates both, proliferation and tumoral growth of cervical cancer, so this should be a possible explanation for the low survival of diabetic patients with cervical cancer in compare to non-diabetic patients with cervical cancer.

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The Potential Oncogenic and MLN4924-Resistant Effects of CSN5 on Cervical Cancer Cells

10.21203/rs.3.rs-550782/v1 ◽

2021 ◽

Author(s):

Huilin Zhang ◽

Ping He ◽

Qing Zhou ◽

Yan Lu ◽

Bingjian Lu

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Cell ◽

Cervical Cancer Cell ◽

Cervical Cancers ◽

Cervical Cancer Cells

Abstract BackgroundsCSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet.MethodsData from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR-CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. CCK8, clone formation assay and cell cycle assay were also employed. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. Moreover, MLN4924 was applied in Siha and Hela with CSN5 overexpression.ResultsWe found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells.ConclusionsOur findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.

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The potential oncogenic and MLN4924-resistant effects of CSN5 on cervical cancer cells

Cancer Cell International ◽

10.1186/s12935-021-02078-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Huilin Zhang ◽

Ping He ◽

Qing Zhou ◽

Yan Lu ◽

Bingjian Lu

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Cell ◽

Cervical Cancer Cell ◽

Cervical Cancers ◽

Cervical Cancer Cells

Abstract Background CSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet. Methods Data from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 and clinical relevance in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR–CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. The biological behaviors were analyzed by CCK8, clone formation assay, 3-D spheroid generation assay and cell cycle assay. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. MLN4924 was given in Siha and Hela with CSN5 overexpression. Results We found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells. Conclusions Our findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.

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Activated pregnane X receptor inhibits cervical cancer cell proliferation and tumorigenicity by inducing G2/M cell-cycle arrest

Cancer Letters ◽

10.1016/j.canlet.2014.01.026 ◽

2014 ◽

Vol 347 (1) ◽

pp. 88-97 ◽

Cited By ~ 10

Author(s):

Yongdong Niu ◽

Ziliang Wang ◽

Haihua Huang ◽

Shuping Zhong ◽

Wenfeng Cai ◽

...

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Cell Proliferation ◽

Cell Cycle Arrest ◽

Cancer Cell ◽

Pregnane X Receptor ◽

Cervical Cancer Cell ◽

Cancer Cell Proliferation ◽

M Cell ◽

Cycle Arrest

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Growth factor progranulin contributes to cervical cancer cell proliferation and transformation in vivo and in vitro

Gynecologic Oncology ◽

10.1016/j.ygyno.2014.05.025 ◽

2014 ◽

Vol 134 (2) ◽

pp. 364-371 ◽

Cited By ~ 18

Author(s):

Yi Lu ◽

Lin Zheng ◽

Wen Zhang ◽

Tingting Feng ◽

Juan Liu ◽

...

Keyword(s):

Cervical Cancer ◽

Cell Proliferation ◽

Growth Factor ◽

Cancer Cell ◽

Cervical Cancer Cell ◽

Cancer Cell Proliferation

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Extracellular Vesicles Long Non-Coding RNA AGAP2-AS1 Contributes to Cervical Cancer Cell Proliferation Through Regulating the miR-3064-5p/SIRT1 Axis

Frontiers in Oncology ◽

10.3389/fonc.2021.684477 ◽

2021 ◽

Vol 11 ◽

Author(s):

Min Li ◽

Jing Wang ◽

Hongli Ma ◽

Li Gao ◽

Kunxiang Zhao ◽

...

Keyword(s):

Cervical Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Cell ◽

Cancer Progression ◽

Molecular Mechanisms ◽

Cervical Cancer Cell ◽

Cancer Cell Proliferation ◽

Cervical Cancer Cells

Cervical cancer is one of the most severe and prevalent female malignancies and a global health issue. The molecular mechanisms underlying cervical cancer development are poorly investigated. As a type of extracellular membrane vesicles, EVs from cancer cells are involved in cancer progression by delivering regulatory factors, such as proteins, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). In this study, we identified an innovative function of extracellular vesicle (EV) lncRNA AGAP2-AS1 in regulating cervical cancer cell proliferation. The EVs were isolated from the cervical cancer cells and were observed by transmission electron microscopy (TEM) and were confirmed by analyzing exosome markers. The depletion of AGAP2-AS1 by siRNA significantly reduced its expression in the exosomes from cervical cancer and in the cervical cancer treated with AGAP2-AS1-knockdown exosomes. The expression of AGAP2-AS1 was elevated in the clinical cervical cancer tissues compared with the adjacent normal tissues. The depletion of EV AGAP2-AS1 reduced cell viabilities and Edu-positive cervical cancer cells, while it enhanced cervical cancer cell apoptosis. Tumorigenicity analysis in nude mice showed that the silencing of EV AGAP2-AS1 attenuated cervical cancer cell growth in vivo. Regarding the mechanism, we identified that AGAP2-AS1 increased SIRT1 expression by sponging miR-3064-5p in cervical cancer cells. The overexpression of SIRT1 or the inhibition of miR-3064-5p reversed EV AGAP2-AS1 depletion-inhibited cancer cell proliferation in vitro. Consequently, we concluded that EV lncRNA AGAP2-AS1 contributed to cervical cancer cell proliferation through regulating the miR-3064-5p/SIRT1 axis. The clinical values of EV lncRNA AGAP2-AS1 and miR-3064-5p deserve to be explored in cervical cancer diagnosis and treatments.

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LncRNA DLEU2 promotes cervical cancer cell proliferation by regulating cell cycle and NOTCH pathway

Experimental Cell Research ◽

10.1016/j.yexcr.2021.112551 ◽

2021 ◽

pp. 112551

Author(s):

Min He ◽

Yitao Wang ◽

Jing Cai ◽

Yan Xie ◽

Chuntao Tao ◽

...

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Cell Proliferation ◽

Cancer Cell ◽

Notch Pathway ◽

Cervical Cancer Cell ◽

Cancer Cell Proliferation

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Hsa_circ_0000520 overexpression increases CDK2 expression via miR-1296 to facilitate cervical cancer cell proliferation

Journal of Translational Medicine ◽

10.1186/s12967-021-02953-9 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Qingling Zheng ◽

Jin Zhang ◽

Ting Zhang ◽

Yanxiang Liu ◽

Xiuluan Du ◽

...

Keyword(s):

Cell Cycle ◽

Cervical Cancer ◽

Cell Proliferation ◽

Cancer Cell ◽

Cell Cycle Progression ◽

Cell Counting ◽

Cervical Cancer Cell ◽

Cancer Cell Proliferation ◽

Loss Of Function ◽

Tissue Samples

Abstract Background Circular RNA (circRNA) has been demonstrated to participate in cervical cancer development. In this study, we analyzed the role of hsa_circ_0000520 in cervical cancer. Methods Fifty-two pairs of cervical cancer and adjacent normal tissue samples were collected, and five human cervical cancer cell lines were obtained followed by the detection of hsa_circ_0000520 expression. Nuclear-cytoplasmic isolation and fluorescence in situ hybridization were performed to analyze the subcellular localization of hsa_circ_0000520 while linear RNA was digested by RNase R. Gain- or loss-of function experiments on hsa_circ_0000520 were performed, followed by detection of cell proliferation and cell cycle by EdU, Cell Counting Kit-8, colony formation assay, and flow cytometry respectively. Results Hsa_circ_0000520 and cyclin-dependent kinase 2 (CDK2) were highly expressed in cervical cancer tissues. Binding sites between microRNA-1296 (miR-1296) and hsa_circ_0000520 or CDK2 were verified. Antibody to Argonaute 2 (Ago2) could precipitate hsa_circ_0000520, indicating that hsa_circ_0000520 could competitively bind to miR-1296 via Ago2. Silencing hsa_circ_0000520 inhibited cervical cancer cell proliferation and promoted the inhibitory effects of miR-1296 on CDK2, thereby blocking cell cycle progression and promoting apoptosis. Conclusion These results support the premise that targeting hsa_circ_0000520 can be a potential approach to combat cervical cancer.

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