miR-29b Derived from Bone Marrow Stromal Cell (BMSC) Exosomes Improves Laryngeal Carcinoma by Inhibiting Forkhead Box Protein P1 (FOXP1) to Decrease Cyclin E2 Transcription

This study intends to investigate whether miR-29b derived from BMSC exosomes (BMSC-exos) affects laryngeal cancer progression. RT-qPCR detected miR-29b level in BMSCs and BMSC-exos. After miR-29b was overexpressed in BMSCs, exos were extracted from BMSCs and used to treat laryngeal cancer cells, followed by CCK-8 assay and soft agar assay. When cells were treated with FOXP1 inhibitor or cyclin E2 vector, Western blot analyzed the expression of related proteins and flow cytometry assessed cell cycle distribution. In vivo experiment was conducted to assess miR-29b’s effect on tumor growth. miR-29b was upregulated in BMSC-exos, but lowly expressed in cancer cells. miR-29b upregulation inhibited the proliferation of laryngeal cancer cells and delayed tumor progression In vivo by inducing cell cycle arrest. Importantly, miR-29b bound 3′UTR of FXOP1 to inhibit its expression, and further reduced cyclin E2 level. sh-FXOP1 or cyclin E2 vector can restore the cell cycle and proliferation caused by miR-29b. In conclusion, miR-29b enriched in BMSC-exo can down-regulate cyclin E2 expression through targeted inhibition of FXOP1, thereby inhibiting the progression of laryngeal cancer.

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Circular RNA circGLIS3 promotes bladder cancer proliferation via the miR-1273f/SKP1/Cyclin D1 axis

Cell Biology and Toxicology ◽

10.1007/s10565-021-09591-3 ◽

2021 ◽

Author(s):

Shuilian Wu ◽

Jialei Yang ◽

Haotian Xu ◽

Xin Wang ◽

Ruirui Zhang ◽

...

Keyword(s):

Cell Cycle ◽

Bladder Cancer ◽

Cyclin D1 ◽

Cancer Cells ◽

Cancer Progression ◽

Migration And Invasion ◽

Multiple Tumor ◽

Bladder Cancer Cells

AbstractExtensive research confirmed that circRNA can play a regulatory role in various stages of tumors by interacting with various molecules. Identifying the differentially expressed circRNA in bladder cancer and exploring its regulatory mechanism on bladder cancer progression are urgent. In this study, we screened out a circRNA-circGLIS3 with a significant upregulation trend in both bladder cancer tissues and cells. Bioinformatics prediction results showed that circGLIS3 may be involved in multiple tumor-related pathways. Function gain and loss experiments verified circGLIS3 can affect the proliferation, migration, and invasion of bladder cancer cells in vitro. Moreover, silencing circGLIS3 inhibited bladder cancer cell growth in vivo. Subsequent research results indicated circGLIS3 regulated the expression of cyclin D1, a cell cycle–related protein, and cell cycle progression. Mechanically, circGLIS3 upregulates the expression of SKP1 by adsorbing miR-1273f and then promotes cyclin D1 expression, ultimately promoting the proliferation of bladder cancer cells. In summary, our study indicates that circGLIS3 plays an oncogene role in the development of bladder cancer and has potential to be a candidate for bladder cancer. Graphical abstract

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Knockdown of PD-L1 in Human Gastric Cancer Cells Inhibits Tumor Progression and Improves the Cytotoxic Sensitivity to CIK Therapy

Cellular Physiology and Biochemistry ◽

10.1159/000460504 ◽

2017 ◽

Vol 41 (3) ◽

pp. 907-920 ◽

Cited By ~ 41

Author(s):

Jing Li ◽

Lujun Chen ◽

Yuqi Xiong ◽

Xiao Zheng ◽

Quanqin Xie ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Cancer Progression ◽

Human Gastric Cancer ◽

Gastric Cancer Cells ◽

Over Expression ◽

Gastric Cancer Cell Lines ◽

Cancer Tissues

Background/Abstract: PD-L1 has been an important target of cancer immunotherapy. We have showed that in human gastric cancer tissues, over-expression of PD-L1 was significantly associated with cancer progression and patients’ postoperative prognoses. However, as of now, how PD-L1 regulates the biological function of gastric cancer cells still remains elusive. Methods: We constructed the stable PD-L1 knockdown expression gastric cancer cell lines by using RNAi method, and further investigated the changes of biological functions including cell viability, migration, invasion, cell cycle, apoptosis, tumorigenicity in vivo, and the cytotoxic sensitivity to CIK therapy, in contrast to the control cells. Results: In the current study, we demonstrated that the knockdown of PD-L1 expression in human gastric cancer cells could significantly suppress the cell proliferation, migration, invasion, apoptosis, cell cycle, tumorigenicity in vivo and the cytotoxic sensitivity to CIK therapy. Conclusion: Our results indicate that PD-L1 contributes towards transformation and progression of human gastric cancer cells, and its intervention could prove to be an important therapeutic strategy against gastric cancer.

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Targeting Lung Cancer Stem Cells with Antipsychological Drug Thioridazine

BioMed Research International ◽

10.1155/2016/6709828 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 14

Author(s):

Haiying Yue ◽

Dongning Huang ◽

Li Qin ◽

Zhiyong Zheng ◽

Li Hua ◽

...

Keyword(s):

Lung Cancer ◽

Cell Cycle ◽

Stem Cells ◽

Cancer Stem Cells ◽

Cancer Progression ◽

Cell Cycle Distribution ◽

Lung Cancer Stem Cells ◽

Sphere Formation

Lung cancer stem cells are a subpopulation of cells critical for lung cancer progression, metastasis, and drug resistance. Thioridazine, a classical neurological drug, has been reported with anticancer ability. However, whether thioridazine could inhibit lung cancer stem cells has never been studied. In our current work, we used different dosage of thioridazine to test its effect on lung cancer stem cells sphere formation. The response of lung cancer stem cells to chemotherapy drug with thioridazine treatment was measured. The cell cycle distribution of lung cancer stem cells after thioridazine treatment was detected. The in vivo inhibitory effect of thioridazine was also measured. We found that thioridazine could dramatically inhibit sphere formation of lung cancer stem cells. It sensitized the LCSCs to chemotherapeutic drugs 5-FU and cisplatin. Thioridazine altered the cell cycle distribution of LCSCs and decreased the proportion of G0 phase cells in lung cancer stem cells. Thioridazine inhibited lung cancer stem cells initiated tumors growth in vivo. This study showed that thioridazine could inhibit lung cancer stem cells in vitro and in vivo. It provides a potential drug for lung cancer therapy through targeting lung cancer stem cells.

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miR-3687 Overexpression Promotes Bladder Cancer Cell Growth Through Inhibiting the Negative Effect of FOXP1 on Cyclin E2 Transcription

10.20944/preprints201809.0545.v1 ◽

2018 ◽

Author(s):

Qipeng Xie ◽

Caiyi Chen ◽

Haiying Li ◽

Huiying Yan ◽

Jiheng Xu ◽

...

Keyword(s):

Cell Cycle ◽

Bladder Cancer ◽

Protein Expression ◽

Cancer Progression ◽

Cancer Cell Growth ◽

Cycle Arrest ◽

Cyclin E2 ◽

Negative Effect

Cyclin E2, a member of the cyclin family, is a key cell cycle-related protein. This protein plays essential roles in cancer progression, and as such, an inhibitor of cyclin E2 has been approved to treat several types of cancers. Even so, mechanisms underlying how to regulate cyclin E2 expression in cancer remain largely unknown. The current study found that miR-3687 is up-regulated in clinical bladder cancer (BC) tumor tissues, TCGA database and human BC cell lines. Inhibition of miR-3687 expression significantly reduces human BC cell proliferation in vitro and tumor growth in vivo, which are concurrently with the induction of G0/G1 cell cycle arrest and downregulation of cyclin E2 protein expression. Interestingly, overexpression of cyclin E2 reversed the inhibition of BC proliferation induced by miR-3687. Mechanistic studies suggest that miR-3687 could bind to the 3'-UTR of foxp1 mRNA, downregulates FOXP1 protein expression, and in turn promotes the transcription of cyclin E2, thereby promoting the growth of BC cells. Collectively, the current study not only establishes a novel regulatory axis of miR-3687/FOXP1 in regard to regulation of cyclin E2 expression in BC cells, but also provides strong suggestive evidence that miR-3687 and FOXP1 may be potentially promising targets in therapeutic strategies of human BC.

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Titanium dioxide nanoparticles induce endoplasmic reticulum stress-mediated apoptotic cell death in liver cancer cells

Journal of International Medical Research ◽

10.1177/0300060520903652 ◽

2020 ◽

Vol 48 (4) ◽

pp. 030006052090365

Author(s):

Zhiwang Li ◽

Jingliang He ◽

Bowei Li ◽

Jinqian Zhang ◽

Ke He ◽

...

Keyword(s):

Cell Cycle ◽

Endoplasmic Reticulum ◽

Cell Growth ◽

Liver Cancer ◽

Er Stress ◽

Cancer Cells ◽

Cell Cycle Distribution ◽

Expression Levels ◽

Liver Cancer Cells

Objective Titanium oxide (TiO2) acts as a photosensitizer in photodynamic therapy by mediating reactive oxygen species (ROS)-induced endoplasmic reticulum (ER) stress. This study aimed to investigate the effect of TiO2 on ER stress in liver cancer cells. Methods Normal human liver and human hepatocarcinoma cell lines were incubated with various concentrations of TiO2 nanotubes for 48 hours. Cell growth, apoptosis, cell cycle, and cellular ROS were detected. Expression levels of ER stress sensors (PERK and ATF6) and Bax were evaluated by western blot. The effect of TiO2 on liver cancer growth was also investigated in mice in vivo. Results TiO2 inhibited cell growth, increased apoptosis and cellular ROS levels, and arrested the cell cycle in G1 stage in liver cancer cells. TiO2 also increased PERK, ATF6, and Bax expression levels in liver cancer cells in dose-dependent manners. TiO2 had no significant effect on cell growth, apoptosis, ROS level, cell cycle distribution, or PERK, ATF6, or Bax expression in normal liver cells. TiO2 administration reduced tumor volume and increased PERK, Bax, and ATF6 expression levels in tumor tissues in vivo. Conclusions TiO2 nanoparticles increased ROS-induced ER stress and activated the PERK/ATF6/Bax axis in liver cancer cells in vitro and in vivo.

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Circular RNA FLNA acts as a sponge of miR-486-3p in promoting lung cancer progression via regulating XRCC1 and CYP1A1

Cancer Gene Therapy ◽

10.1038/s41417-021-00293-w ◽

2021 ◽

Author(s):

Jiongwei Pan ◽

Gang Huang ◽

Zhangyong Yin ◽

Xiaoping Cai ◽

Enhui Gong ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Cancer Progression ◽

Lung Cancer Cells ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Related Factors

AbstractSignificantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.

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POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01476-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ronggang Luo ◽

Yi Zhuo ◽

Quan Du ◽

Rendong Xiao

Keyword(s):

Lung Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Cancer Progression ◽

Human Lung ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Cancer Tissues

Abstract Background To detect and investigate the expression of POU domain class 2 transcription factor 2 (POU2F2) in human lung cancer tissues, its role in lung cancer progression, and the potential mechanisms. Methods Immunohistochemical (IHC) assays were conducted to assess the expression of POU2F2 in human lung cancer tissues. Immunoblot assays were performed to assess the expression levels of POU2F2 in human lung cancer tissues and cell lines. CCK-8, colony formation, and transwell-migration/invasion assays were conducted to detect the effects of POU2F2 and AGO1 on the proliferaion and motility of A549 and H1299 cells in vitro. CHIP and luciferase assays were performed for the mechanism study. A tumor xenotransplantation model was used to detect the effects of POU2F2 on tumor growth in vivo. Results We found POU2F2 was highly expressed in human lung cancer tissues and cell lines, and associated with the lung cancer patients’ prognosis and clinical features. POU2F2 promoted the proliferation, and motility of lung cancer cells via targeting AGO1 in vitro. Additionally, POU2F2 promoted tumor growth of lung cancer cells via AGO1 in vivo. Conclusion We found POU2F2 was highly expressed in lung cancer cells and confirmed the involvement of POU2F2 in lung cancer progression, and thought POU2F2 could act as a potential therapeutic target for lung cancer.

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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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Fibroblast activation protein targeted near infrared photoimmunotherapy (NIR PIT) overcomes therapeutic resistance in human esophageal cancer

Scientific Reports ◽

10.1038/s41598-021-81465-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ryoichi Katsube ◽

Kazuhiro Noma ◽

Toshiaki Ohara ◽

Noriyuki Nishiwaki ◽

Teruki Kobayashi ◽

...

Keyword(s):

Esophageal Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Near Infrared ◽

Fibroblast Activation Protein ◽

Therapeutic Resistance ◽

Fibroblast Activation ◽

Human Esophageal Cancer

AbstractCancer-associated fibroblasts (CAFs) have an important role in the tumor microenvironment. CAFs have the multifunctionality which strongly support cancer progression and the acquisition of therapeutic resistance by cancer cells. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that uses a highly selective monoclonal antibody (mAb)-photosensitizer conjugate. We developed fibroblast activation protein (FAP)-targeted NIR-PIT, in which IR700 was conjugated to a FAP-specific antibody to target CAFs (CAFs-targeted NIR-PIT: CAFs-PIT). Thus, we hypothesized that the control of CAFs could overcome the resistance to conventional chemotherapy in esophageal cancer (EC). In this study, we evaluated whether EC cell acquisition of stronger malignant characteristics and refractoriness to chemoradiotherapy are mediated by CAFs. Next, we assessed whether the resistance could be rescued by eliminating CAF stimulation by CAFs-PIT in vitro and in vivo. Cancer cells acquired chemoradiotherapy resistance via CAF stimulation in vitro and 5-fluorouracil (FU) resistance in CAF-coinoculated tumor models in vivo. CAF stimulation promoted the migration/invasion of cancer cells and a stem-like phenotype in vitro, which were rescued by elimination of CAF stimulation. CAFs-PIT had a highly selective effect on CAFs in vitro. Finally, CAF elimination by CAFs-PIT in vivo demonstrated that the combination of 5-FU and NIR-PIT succeeded in producing 70.9% tumor reduction, while 5-FU alone achieved only 13.3% reduction, suggesting the recovery of 5-FU sensitivity in CAF-rich tumors. In conclusion, CAFs-PIT could overcome therapeutic resistance via CAF elimination. The combined use of novel targeted CAFs-PIT with conventional anticancer treatments can be expected to provide a more effective and sensible treatment strategy.

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Reduced Lamin A/C does Not Facilitate Cancer Cell Transendothelial Migration but Compromises Lung Metastasis

Cancers ◽

10.3390/cancers13102383 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2383

Author(s):

Francesco Roncato ◽

Ofer Regev ◽

Sara W. Feigelson ◽

Sandeep Kumar Yadav ◽

Lukasz Kaczmarczyk ◽

...

Keyword(s):

Cancer Cells ◽

Lung Metastasis ◽

Metastatic Cancer ◽

Nuclear Lamina ◽

Transendothelial Migration ◽

Soft Agar ◽

Lamin A ◽

And Migration

The mechanisms by which the nuclear lamina of tumor cells influences tumor growth and migration are highly disputed. Lamin A and its variant lamin C are key lamina proteins that control nucleus stiffness and chromatin conformation. Downregulation of lamin A/C in two prototypic metastatic lines, B16F10 melanoma and E0771 breast carcinoma, facilitated cell squeezing through rigid pores, and reduced heterochromatin content. Surprisingly, both lamin A/C knockdown cells grew poorly in 3D spheroids within soft agar, and lamin A/C deficient cells derived from spheroids transcribed lower levels of the growth regulator Yap1. Unexpectedly, the transendothelial migration of both cancer cells in vitro and in vivo, through lung capillaries, was not elevated by lamin A/C knockdown and their metastasis in lungs was even dramatically reduced. Our results are the first indication that reduced lamin A/C content in distinct types of highly metastatic cancer cells does not elevate their transendothelial migration (TEM) capacity and diapedesis through lung vessels but can compromise lung metastasis at a post extravasation level.

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