scholarly journals Alternative splicing regulation of cell cycle genes by SPF45/SR140/CHERP complex controls cell proliferation

RNA ◽  
2021 ◽  
pp. rna.078935.121
Author(s):  
Elena Martin ◽  
Claudia Vivori ◽  
Malgorzata Rogalska ◽  
Jorge Herrero ◽  
Juan Valcarcel
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Alternative Splicing ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Splicing Factors ◽  
Splicing Regulation ◽  
Cancer Cell Proliferation ◽  
Cycle Progression ◽  
Regulation Of Cell Cycle

The regulation of pre-mRNA processing has important consequences for cell division and the control of cancer cell proliferation but the underlying molecular mechanisms remain poorly understood. We report that three splicing factors, SPF45, SR140 and CHERP form a tight physical and functionally coherent complex that regulates a variety of alternative splicing events, frequently by repressing short exons flanked by suboptimal 3' splice sites. These comprise alternative exons embedded in genes with important functions in cell cycle progression, including the G2/M key regulator FOXM1 and the spindle regulator SPDL1. Knockdown of either of the three factors leads to G2/M arrest and to enhanced apoptosis in HeLa cells. Promoting the changes in FOXM1 or SPDL1 splicing induced by SPF45/SR140/CHERP knockdown partially recapitulate the effects on cell growth, arguing that the complex orchestrates a program of alternative splicing necessary for efficient cell proliferation.

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 Mechanosensitive Expression of Lamellipodin Governs Cell Cycle Progression and Intracellular Stiffness

2020 ◽  
Author(s):  
Joseph A. Brazzo ◽  
Kwonmoo Lee ◽  
Yongho Bae
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Cycle Progression ◽  
Cellular Processes ◽  
M Phase ◽  
And Migration ◽  
In Cells

SUMMARYCells exhibit pathological behaviors in response to increased extracellular matrix (ECM) stiffness, including accelerated cell proliferation and migration [1–9], which are correlated with increased intracellular stiffness and tension [2, 3, 10–12]. The biomechanical signal transduction of ECM stiffness into relevant molecular signals and resultant cellular processes is mediated through multiple proteins associated with the actin cytoskeleton in lamellipodia [2, 3, 10, 11, 13]. However, the molecular mechanisms by which lamellipodial dynamics regulate cellular responses to ECM stiffening remain unclear. Previous work described that lamellipodin, a phosphoinositide- and actin filament-binding protein that is known mostly for controlling cell migration [14–21], promotes ECM stiffness-mediated early cell cycle progression [2], revealing a potential commonality between the mechanisms controlling stiffness-dependent cell migration and those controlling cell proliferation. However, i) whether and how ECM stiffness affects the levels of lamellipodin expression and ii) whether stiffness-mediated lamellipodin expression is required throughout cell cycle progression and for intracellular stiffness have not been explored. Here, we show that the levels of lamellipodin expression in cells are significantly increased by a stiff ECM and that this stiffness-mediated lamellipodin upregulation persistently stimulates cell cycle progression and intracellular stiffness throughout the cell cycle, from the early G1 phase to M phase. Finally, we show that both Rac activation and intracellular stiffening are required for the mechanosensitive induction of lamellipodin. More specifically, inhibiting Rac1 activation in cells on stiff ECM reduces the levels of lamellipodin expression, and this effect is reversed by the overexpression of activated Rac1 in cells on soft ECM. We thus propose that lamellipodin is a critical molecular lynchpin in the control of mechanosensitive cell cycle progression and intracellular stiffness.

scholarly journals LncRNA EPIC1 Promotes Cancer Cell Proliferation and Inhibits Apoptosis in Gallbladder Cancer Interacting with lncRNA LET

2020 ◽  
Author(s):  
Changbo Fu ◽  
Lei Nie ◽  
Tao Yin ◽  
Xuan Xu ◽  
weijun lu
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Gallbladder Cancer ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Human Cancer ◽  
Cancer Cell Proliferation ◽  
Cycle Progression ◽  
Tumor Tissues ◽  
Proliferation And Apoptosis

Abstract Background: LncRNA EPIC1 is likely involved in human cancer by promoting cell cycle progression. Our study was carried out to investigate the involvement of EPIC1 in gallbladder cancer (GBC). Methods: Expression levels of EPIC1 in two types of tissues (GBC and paracancerous) and plasma were measured by performing qPCR. GBC-SD and SGC-996 cells were transfected with LET and EPIC1 expression vectors.Results: In the preset study we found that EPIC1 was upregulated in tumor tissues than in paracancerous tissues of GBC patients, and plasma levels of EPIC1 were significantly correlated with levels of EPIC1 in tumor tissues. LncRNA LET was downregulated in tumor tissues than in paracancerous tissues and was inversely correlated with EPIC1 in both tumor tissues and paracancerous tissues. Overexpression of EPIC1 led to downregulated LET, and LET overexpression also mediated the downregulation of EPIC1. EPIC1 led to accelerated GBC cell proliferation and inhibited apoptosis. Overexpression of LET played opposites roles. In addition, overexpression of LET also attenuated the effects of EPIC1 overexpression on cancer cell proliferation and apoptosis. Conclusion: Therefore, therefore, lncRNA EPIC1 may promote cancer cell proliferation and inhibit apoptosis in GBC by interacting with LET.

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