scholarly journals SATB2-AS1 acts as miR-299-3p sponge to facilitate tumorigenesis in human non-small cell lung cancer

2021 ◽  
Author(s):  
Xiaofeng Wu ◽  
Junti Lu ◽  
Wen Chen ◽  
Meng Liang ◽  
Nan Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Tumor Cell Proliferation ◽  
Small Cell Lung ◽  
Cycle Progression

IntroductionNon-small cell lung cancer (NSCLC), the most common pathological type of lung cancer, is partly responsible for an increasing number of tumor-related deaths worldwide. This study aimed to explore the biological role of the anti-sense transcript of special AT-rich sequence binding protein 2 (SATB2-AS1), a novel cancer-related long non-coding RNA (lncRNA), and illustrate the potential molecular mechanisms.Material and methodsThe expression patterns of SATB2-AS1 were determined via qPCR analysis in clinical samples and tumor cell lines. Kaplan-Meier survival analysis was conducted to assess the relationship between SATB2-AS1 expression and survival time of NSCLC patients. NSCLC tumors were transfected with SATB2-AS1 expression vectors or specific short hairpin RNAs (sh-SATB2-AS1). Tumor cell proliferation, cell cycle progression and apoptosis was detected by MTT assays and flow cytometric method, respectively. Nude mouse transplantation models were applied to investigate the effects of SATB2-AS1 on tumor cell growth in vivo. Bio-informatics analysis, luciferase reporter assays and rescue assays were performed to elucidate possible molecular mechanisms.ResultsSATB2-AS1 up-regulation was observed in tumorous tissues and cell lines. Up-regulated SATB2-AS1 expression was associated with shorter overall survival time of patients. SATB2-AS1 over-expression facilitated tumor cell proliferation, cell cycle progression and survival, while its knockdown inhibited tumor cell proliferation, cell cycle progression and survival. SATB2-AS1 depletion suppressed tumor growth in vivo. SATB2-AS1 was revealed to act as a miR-299-3p sponge to exert carcinogenic role.ConclusionsOur data indicate that SATB2-AS1 acts as a miR-299-3p sponge to facilitate NSCLC development, providing a novel candidate therapeutic target for NSCLC.

CKS2 Promotes the Growth in Non-Small-Cell Lung Cancer by Downregulating Cyclin-Dependent Kinase Inhibitor

Pathobiology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Zongren Wan ◽  
Lixin Wang ◽  
Dan Yang ◽  
Pengling Li ◽  
Qing Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Growth ◽  
Small Cell Lung Cancer ◽  
Cell Cycle Progression ◽  
Small Cell ◽  
Cyclin Dependent Kinase ◽  
Small Cell Lung ◽  
Cycle Progression

<b><i>Introduction/Objective:</i></b> This study aimed to explore the expression of cyclin-dependent kinase subunit 2 (CKS2) in tissues and cells in non-small-cell lung cancer (NSCLC) and the function mechanism of CKS2 in NSCLC cell growth and tumorigensis. <b><i>Methods:</i></b> After transfecting NCI-H2170 cells with short-hair RNA (shRNA), an shCKS2 gene-silencing model was established. The cells were divided into a shRNA group and shNC group. For overexpression cell lines, we used the same method to establish the NCI-H2170-CKS2 cell lines. Cell Count Kit-8 assay and colony formation assay were used to determine cell viability and cell growth, respectively. Propidium iodide staining was used to determine cell cycle progression. The mRNA expression of CKS2 and protein expression of CKS2, p21, p53, and PTEN were determined by RT-qPCR and Western blotting, respectively. The expression of CKS2, p53, and Ki67 in tissues was determined by immunohistochemical stain. The in vivo tumorigenesis assays were used to determine the ability of CKS2 in tumor growth. <b><i>Results:</i></b> The results of RT-qPCR and Western blotting assay revealed that CKS2 upregulated expression in NSCLC tissues and cells. The results of the CCK-8 assay revealed that the shRNA group exhibited significantly lower cell viability and foci formation than the empty plasmid group, while CKS2 overexpression induces cell growth and cell cycle progression. The result of nude mice suggested that CKS2 knockdown expression suppressed tumorigenesis in the in vivo animal model. <b><i>Conclusions:</i></b> Our study suggests that CKS2 could be a biomarker in the progression and prognosis of NSCLC.

scholarly journals LMNB2 promotes the progression of colorectal cancer by silencing p21 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Chen-Hua Dong ◽  
Tao Jiang ◽  
Hang Yin ◽  
Hu Song ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Gene Set Enrichment Analysis ◽  
Molecular Therapy ◽  
Cycle Progression ◽  
Cancer Tissues

AbstractColorectal cancer is the second common cause of death worldwide. Lamin B2 (LMNB2) is involved in chromatin remodeling and the rupture and reorganization of nuclear membrane during mitosis, which is necessary for eukaryotic cell proliferation. However, the role of LMNB2 in colorectal cancer (CRC) is poorly understood. This study explored the biological functions of LMNB2 in the progression of colorectal cancer and explored the possible molecular mechanisms. We found that LMNB2 was significantly upregulated in primary colorectal cancer tissues and cell lines, compared with paired non-cancerous tissues and normal colorectal epithelium. The high expression of LMNB2 in colorectal cancer tissues is significantly related to the clinicopathological characteristics of the patients and the shorter overall and disease-free cumulative survival. Functional analysis, including CCK8 cell proliferation test, EdU proliferation test, colony formation analysis, nude mouse xenograft, cell cycle, and apoptosis analysis showed that LMNB2 significantly promotes cell proliferation by promoting cell cycle progression in vivo and in vitro. In addition, gene set enrichment analysis, luciferase report analysis, and CHIP analysis showed that LMNB2 promotes cell proliferation by regulating the p21 promoter, whereas LMNB2 has no effect on cell apoptosis. In summary, these findings not only indicate that LMNB2 promotes the proliferation of colorectal cancer by regulating p21-mediated cell cycle progression, but also suggest the potential value of LMNB2 as a clinical prognostic marker and molecular therapy target.

scholarly journals Gastric Adenocarcinoma Predictive Long Intergenic Non-Coding RNA Promotes Tumor Occurrence and Progression in Non-Small Cell Lung Cancer via Regulation of the miR-661/eEF2K Signaling Pathway

2018 ◽  
Vol 51 (5) ◽  
pp. 2136-2147 ◽  
Author(s):  
Haiting Gu ◽  
Junfeng Chen ◽  
Yukang Song ◽  
Haiyan Shao
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Western Blot ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Non Coding Rna

Background/Aims: Long non-coding RNAs (lncRNAs) play vital roles in carcinogenesis as oncogenes or tumor suppressor genes. This study explored the biological function of lncRNA gastric adenocarcinoma predictive long intergenic non-coding RNA (GAPLINC) in human non-small cell lung cancer (NSCLC). Methods: GAPLINC expression in NSCLC specimens and cell lines was detected by qRT-PCR and Western blot. The effect of GAPLINC on cell proliferation was investigated using CCK8-assay, colony formation assay, and xenograft model. The effects of GAPLINC on apoptosis and cell cycle were determined using flow cytometry. The mechanism of GAPLINC involved in NSCLC was explored using Western blot, luciferase reporter assay, and RNA fluorescence in situ hybridization. Results: We found that GAPLINC expression was up-regulated in NSCLC tissues and cell lines. Overexpression of GAPLINC was associated with poor prognosis in patients with NSCLC. Silencing of GAPLINC significantly inhibited cell proliferation, promoted apoptosis, and induced cell cycle arrest in the G0/G1 phase. Results from xenograft transplantation showed that GAPLINC silencing inhibited the tumor growth in vivo. Interestingly, GAPLINC silencing decreased the expression of eukaryotic elongation factor-2 kinase (eEF2K) protein both in vivo and in vitro. Bioinformatic analysis and luciferase reporter confirmed that miR-661 targeted GAPLINC and eEF2K 3’-UTR and was negatively correlated with the expression of GAPLINC and eEF2K. Conclusion: Our findings indicate that GAPLINC promotes NSCLC tumorigenesis by regulating miR-661/eEF2K cascade and provide new insights for the pathogenesis underlying NSCLC and potential targets for therapeutic strategy.

scholarly journals Roquin1 Suppresses Breast Cancer Growth by Inducing Cell Cycle Arrest via Selectively Destabilizing Cell Cycle–Promoting Gene mRNAs

2020 ◽  
Author(s):  
Wenbao Lu ◽  
Meicen Zhou ◽  
Bing Wang ◽  
Xueting Liu ◽  
Bingwei Li
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Breast Cancer Cell ◽  
Breast Tumor ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Cycle Arrest

Abstract Background: Dysregulation of cell cycle progression is one of the common features of human cancer cells, however, its mechanism remains unclear. This study aims to clarify the role and the underlying mechanisms of Roquin1 in cell cycle arrest induction in breast cancer.Methods: Public cancer databases were analyzed to identify the expression pattern of Roquin1 in human breast cancers and the significant association with patient survival. Quantitative real-time PCR and western blots were performed to detect the expression of Roquin1 in breast cancer samples and cell lines. Cell counting, MTT assay, flow cytometry, and in vivo study were conducted to investigate the effects of Roquin1 on cell proliferation, cell cycle progression and tumor progression. RNA-sequencing was applied to identify the differential genes and pathways regulated by Roquin1. RNA immunoprecipitation assay, luciferase reporter assay, mRNA half-life detection, RNA affinity binding assay, and RIP-ChIP were used to explore the molecular mechanisms of Roquin1.Results: We showed that Roquin1 expression in breast cancer tissues and cell lines was inhibited, and the reduction in Roquin1 expression was associated with poor overall survival and relapse free survival of patients with breast cancer. Roquin1 overexpression inhibited breast cancer cell proliferation and induced G1/S cell cycle arrest without causing significant apoptosis. In contrast, knockdown of Roquin1 promoted breast cancer cell growth and cycle progression. Moreover, in vivo induction of Roquin1 by adenovirus significantly suppressed breast tumor growth and metastasis. Mechanistically, Roquin1 selectively destabilizing cell cycle–promoting genes, including Cyclin D1, Cyclin E1, cyclin dependent kinase 6 (CDK6) and minichromosome maintenance 2 (MCM2) through targeting the stem–loop structure in the 3’untranslated region (3’UTR) of mRNAs via its ROQ domain, leading to the downregulation of cell cycle–promoting mRNAs.Conclusions: Our findings demonstrated that Roquin1 was a novel breast tumor suppressor and could induce G1/S cell cycle arrest by selectively downregulating the expression of cell cycle–promoting genes, which might as a potential molecular target for breast cancer treatment.

scholarly journals Fstl1 Promotes Glioma Growth Through the BMP4/Smad1/5/8 Signaling Pathway

2017 ◽  
Vol 44 (4) ◽  
pp. 1616-1628 ◽  
Author(s):  
Xin Jin ◽  
Er Nie ◽  
Xu Zhou ◽  
Ailiang Zeng ◽  
Tianfu Yu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Colony Formation ◽  
Cell Cycle Progression ◽  
Malignant Gliomas ◽  
Treatment Strategies ◽  
Cycle Progression ◽  
Glioma Growth

Background: Gliomas result in the highest morbidity and mortality rates of intracranial primary central nervous system tumors because of their aggressive growth characteristics and high postoperative recurrence. They are characterized by genetic instability, intratumoral histopathological variability and unpredictable clinical behavior in patients. Proliferation is a key aspect of the clinical progression of malignant gliomas, complicating complete surgical resection and enabling tumor regrowth and further proliferation of the surviving tumor cells. Methods: The expression of Fstl1 was detected by western blotting and qRT-PCR. We used cell proliferation and colony formation assays to measure proliferation. Then, flow cytometry was used to analyze cell cycle progression. The expression of Fstl1, p-Smad1/5/8 and p21 in GBM tissue sections was evaluated using immunohistochemical staining. Furthermore, we used coimmunoprecipitation (Co-IP) and immunoprecipitation to validate the relationship between Fstl1, BMP4 and BMPR2. Finally, we used orthotopic xenograft studies to measure the growth of tumors in vivo. Results: We found that follistatin-like 1 (Fstl1) was upregulated in high-grade glioma specimens and that its levels correlated with poor prognosis. Fstl1 upregulation increased cell proliferation, colony formation and cell cycle progression, while its knockdown inhibited these processes. Moreover, Fstl1 interacted with bone morphogenetic protein (BMP) 4, but not BMP receptor (BMPR) 2, and competitively inhibited their association. Furthermore, Fstl1 overexpression suppressed the activation of the BMP4/Smad1/5/8 signaling pathway, while BMP4 overexpression reversed this effect. Conclusion: Our study demonstrated that Fstl1 promoted glioma growth through the BMP4/Smad1/5/8 signaling pathway, and these findings suggest potential new glioblastoma treatment strategies.

scholarly journals Tumor quiescence: elevating SOX2 in diverse tumor cell types downregulates a broad spectrum of the cell cycle machinery and inhibits tumor growth

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ethan P. Metz ◽  
Erin L. Wuebben ◽  
Phillip J. Wilder ◽  
Jesse L. Cox ◽  
Kaustubh Datta ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Cell Cycle Machinery

Abstract Background Quiescent tumor cells pose a major clinical challenge due to their ability to resist conventional chemotherapies and to drive tumor recurrence. Understanding the molecular mechanisms that promote quiescence of tumor cells could help identify therapies to eliminate these cells. Significantly, recent studies have determined that the function of SOX2 in cancer cells is highly dose dependent. Specifically, SOX2 levels in tumor cells are optimized to promote tumor growth: knocking down or elevating SOX2 inhibits proliferation. Furthermore, recent studies have shown that quiescent tumor cells express higher levels of SOX2 compared to adjacent proliferating cells. Currently, the mechanisms through which elevated levels of SOX2 restrict tumor cell proliferation have not been characterized. Methods To understand how elevated levels of SOX2 restrict the proliferation of tumor cells, we engineered diverse types of tumor cells for inducible overexpression of SOX2. Using these cells, we examined the effects of elevating SOX2 on their proliferation, both in vitro and in vivo. In addition, we examined how elevating SOX2 influences their expression of cyclins, cyclin-dependent kinases (CDKs), and p27Kip1. Results Elevating SOX2 in diverse tumor cell types led to growth inhibition in vitro. Significantly, elevating SOX2 in vivo in pancreatic ductal adenocarcinoma, medulloblastoma, and prostate cancer cells induced a reversible state of tumor growth arrest. In all three tumor types, elevation of SOX2 in vivo quickly halted tumor growth. Remarkably, tumor growth resumed rapidly when SOX2 returned to endogenous levels. We also determined that elevation of SOX2 in six tumor cell lines decreased the levels of cyclins and CDKs that control each phase of the cell cycle, while upregulating p27Kip1. Conclusions Our findings indicate that elevating SOX2 above endogenous levels in a diverse set of tumor cell types leads to growth inhibition both in vitro and in vivo. Moreover, our findings indicate that SOX2 can function as a master regulator by controlling the expression of a broad spectrum of cell cycle machinery. Importantly, our SOX2-inducible tumor studies provide a novel model system for investigating the molecular mechanisms by which elevated levels of SOX2 restrict cell proliferation and tumor growth.

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