A Positive Feedback Loop Comprising LHW–TMO5 and Local Auxin Biosynthesis Regulates Initial Vascular Development in Arabidopsis Roots

2019 ◽  
Vol 60 (12) ◽  
pp. 2684-2691 ◽  
Author(s):  
Kyoko Ohashi-Ito ◽  
Kuninori Iwamoto ◽  
Yoshinobu Nagashima ◽  
Mikiko Kojima ◽  
Hitoshi Sakakibara ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Auxin Transport ◽  
Vascular Development ◽  
Fine Tuning ◽  
Root Apical Meristem ◽  
Auxin Biosynthesis ◽  
Positive Feedback Loop ◽  
Vascular Cell

Abstract The phytohormone auxin governs various developmental processes in plants including vascular formation. Auxin transport and biosynthesis are important factors in determining auxin distribution in tissues. Although the role of auxin transport in vein pattern formation is widely recognized, that of auxin biosynthesis in vascular development is poorly understood. Heterodimer complexes comprising two basic helix–loop–helix protein families, LONESOME HIGHWAY (LHW) and TARGET OF MONOPTEROS5 (TMO5)/TMO5-LIKE1 (T5L1), are master transcriptional regulators of the initial process of vascular development. The LHW–TMO5/T5L1 dimers regulate vascular initial cell production, vascular cell proliferation and xylem fate determination in the embryo and root apical meristem (RAM). In this study, we investigated the function of local auxin biosynthesis in initial vascular development in RAM. Results showed that LHW–T5L1 upregulated the expression of YUCCA4 (YUC4), a key auxin biosynthesis gene. The expression of YUC4 was essential for promoting xylem differentiation and vascular cell proliferation in RAM. Conversely, auxin biosynthesis was required for maintaining the expression levels of LHW, TMO5/T5L1 and their targets. Our results suggest that local auxin biosynthesis forms a positive feedback loop for fine-tuning the level of LHW–TMO5/T5L1, which is necessary for initiating vascular development.

scholarly journals CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 contributes to prostate carcinogenesis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jin-Chun Qi ◽  
Zhan Yang ◽  
Tao Lin ◽  
Long Ma ◽  
Ya-Xuan Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Transcriptional Activation ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Biological Effects ◽  
Therapeutic Benefit ◽  
Loss Of Function ◽  
Positive Feedback Loop

Abstract Background Both E2F transcription factor and cyclin-dependent kinases (CDKs), which increase or decrease E2F activity by phosphorylating E2F or its partner, are involved in the control of cell proliferation, and some circRNAs and miRNAs regulate the expression of E2F and CDKs. However, little is known about whether dysregulation among E2Fs, CDKs, circRNAs and miRNAs occurs in human PCa. Methods The expression levels of CDK13 in PCa tissues and different cell lines were determined by quantitative real-time PCR and Western blot analysis. In vitro and in vivo assays were preformed to explore the biological effects of CDK13 in PCa cells. Co-immunoprecipitation anlysis coupled with mass spectrometry was used to identify E2F5 interaction with CDK13. A CRISPR-Cas9 complex was used to activate endogenous CDK13 and circCDK13 expression. Furthermore, the mechanism of circCDK13 was investigated by using loss-of-function and gain-of-function assays in vitro and in vivo. Results Here we show that CDK13 is significantly upregulated in human PCa tissues. CDK13 depletion and overexpression in PCa cells decrease and increase, respectively, cell proliferation, and the pro-proliferation effect of CDK13 is strengthened by its interaction with E2F5. Mechanistically, transcriptional activation of endogenous CDK13, but not the forced expression of CDK13 by its expression vector, remarkably promotes E2F5 protein expression by facilitating circCDK13 formation. Further, the upregulation of E2F5 enhances CDK13 transcription and promotes circCDK13 biogenesis, which in turn sponges miR-212-5p/449a and thus relieves their repression of the E2F5 expression, subsequently leading to the upregulation of E2F5 expression and PCa cell proliferation. Conclusions These findings suggest that CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 is responsible for PCa development. Targeting this newly identified regulatory axis may provide therapeutic benefit against PCa progression and drug resistance.

scholarly journals The Dickkopf1 and FOXM1 positive feedback loop promotes tumor growth in pancreatic and esophageal cancers

Oncogene ◽  
2021 ◽  
Author(s):  
Hirokazu Kimura ◽  
Ryota Sada ◽  
Naoki Takada ◽  
Akikazu Harada ◽  
Yuichiro Doki ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wnt Signaling ◽  
Cancer Cell ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Ductal Adenocarcinoma ◽  
Cancer Cell Proliferation ◽  
Positive Feedback Loop ◽  
Dkk1 Expression ◽  
Foxm1 Expression

AbstractDickkopf1 (DKK1) is overexpressed in various cancers and promotes cancer cell proliferation by binding to cytoskeleton-associated protein 4 (CKAP4). However, the mechanisms underlying DKK1 expression are poorly understood. RNA sequence analysis revealed that expression of the transcription factor forkhead box M1 (FOXM1) and its target genes concordantly fluctuated with expression of DKK1 in pancreatic ductal adenocarcinoma (PDAC) cells. DKK1 knockdown decreased FOXM1 expression and vice versa in PDAC and esophageal squamous cell carcinoma (ESCC) cells. Inhibition of either the DKK1-CKAP4-AKT pathway or the ERK pathway suppressed FOXM1 expression, and simultaneous inhibition of both pathways showed synergistic effects. A FOXM1 binding site was identified in the 5ʹ-untranslated region of the DKK1 gene, and its depletion decreased DKK1 expression and cancer cell proliferation. Clinicopathological and database analysis revealed that PDAC and ESCC patients who simultaneously express DKK1 and FOXM1 have a poorer prognosis. Multivariate analysis demonstrated that expression of both DKK1 and FOXM1 is the independent prognostic factor in ESCC patients. Although it has been reported that FOXM1 enhances Wnt signaling, FOXM1 induced DKK1 expression independently of Wnt signaling in PDAC and ESCC cells. These results suggest that DKK1 and FOXM1 create a positive feedback loop to promote cancer cell proliferation.

P53/miR-34a/SIRT1 Positive Feedback Loop regulates cell proliferation and promotes cell apoptosis in the termination stage of liver regeneration.

2021 ◽  
Author(s):  
Junhua Gong ◽  
Minghua Cong ◽  
Hao Wu ◽  
Menghao Wang ◽  
He Bai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Liver Regeneration ◽  
Positive Feedback ◽  
Cell Apoptosis ◽  
Feedback Loop ◽  
Late Phase ◽  
Liver Weight ◽  
Positive Feedback Loop ◽  
And Function ◽  
Shed Light

Abstract Background The capacity of the liver to restore its architecture and function assures good prognoses of patients who suffer serious hepatic injury or cancer resection. In our study, we found that the P53/miR-34a/SIRT1 positive feedback loop has a remarkable negative regulatory effect, which is related to the termination of liver regeneration. Here, we described how P53/miR-34a/SIRT1 positive feedback loop controls liver regeneration and its possible relationship with liver cancer.Method We performed partial hepatectomy (PH) in mice transfected with adenovirus (Ade) overexpressing P53 and adenovirus-associated virus (AAV) knock-downing miR-34a. LR was analyzed by liver weight/body weight, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and cell proliferation, and the related cellular signals were investigated. Bile acid (BA) levels during LR were analyzed by metabolomics of bile acids. Results We found that the P53/miR-34a/SIRT1 positive feedback loop was activated in the late phase of LR. Overexpression of P53 terminated LR early and enhanced P53/miR-34a/SIRT1 positive feedback loop expression and its proapoptotic effect. Mice from the Ade-P53 group showed smaller livers and higher levels of serum ALT and AST than control mice. While knock-down of miR-34a abolished P53/miR-34a/SIRT1 positive feedback loop during LR. Mice from anti-miR-34a group showed larger livers and lower levels of PCNA-positive cells than control mice. T-β-MCA increased gradually during LR and peaked at 7 days after PH. T-β-MCA inhibited cell proliferation and promoted cell apoptosis via facilitating the P53/miR-34a/SIRT1 positive feedback loop during LR by suppressing FXR/SHP. Conclusion The P53/miR-34a/SIRT1 positive feedback loop plays an important role in the termination of LR. Our findings shed light on the molecular and metabolic mechanisms of LR termination and provide a potential therapeutic alternative for treating P53-wild-type HCC patients.

scholarly journals ALYREF Drives Cancer Cell Proliferation Through an ALYREF-MYC Positive Feedback Loop in Glioblastoma

2021 ◽  
Vol Volume 14 ◽  
pp. 145-155
Author(s):  
Jianjun Wang ◽  
Yuchen Li ◽  
Binbin Xu ◽  
Jiao Dong ◽  
Haiyan Zhao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Cancer Cell Proliferation ◽  
Positive Feedback Loop

The Wnt/β-catenin/VASP positive feedback loop drives cell proliferation and migration in breast cancer

Oncogene ◽  
2019 ◽  
Vol 39 (11) ◽  
pp. 2258-2274 ◽  
Author(s):  
Kai Li ◽  
Jingwei Zhang ◽  
Yihao Tian ◽  
Yanqi He ◽  
Xiaolong Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Positive Feedback Loop ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals The interplay between ATF2 and NEAT1 contributes to lung adenocarcinoma progression

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jian Liu ◽  
Kai Li ◽  
Rui Wang ◽  
Sisi Chen ◽  
Jie Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Transcription Factor ◽  
Lung Adenocarcinoma ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Tumor Model ◽  
Luciferase Reporter ◽  
Activator Protein 1 ◽  
Positive Feedback Loop ◽  
Rna Immunoprecipitation

Abstract Background Activating transcription factor 2 (ATF2), a member of the activator protein 1 (AP-1) transcription factor family, has been shown to be involved in the pathobiology of numerous cancers. However, the biological role and mechanism of ATF2 in lung adenocarcinoma (LUAD) remains to be elucidated. Methods The expression of ATF2, NEAT1 and miR-26a-5p in LUAD tissues and cell lines was detected by qRT-PCR and western blotting. The interaction between ATF2, NEAT1, and miR-26a-5p was validated by chromatin immunoprecipitation, luciferase reporter assay and RNA immunoprecipitation. Cell proliferation, invasion and tumorigenesis of LUAD cells were analyzed by using CCK8, transwell invasion assay and xenograft tumor model. Results We confirmed that ATF2 expression was increased in LUAD tissues compared with normal adjacent lung tissues. Functional experiments showed that ATF2 positively regulated cell proliferation and invasion in LUAD cells. Moreover, we identified that NEAT1 expression was increased in LUAD tissues and positively correlated with ATF2 expression. Mechanistically, ATF2 could bind to the promoter of NEAT1 to promote its transcription. Rescue experiments showed that ATF2 exerted its oncogenic function in LUAD, at least, partly through NEAT1 upregulation. In turn, NEAT1 could positively regulate ATF2 expression and form a positive feedback loop in LUAD cells. Furthermore, we demonstrated that NEAT1 positively regulated ATF2 expression via sponging miR-26a-5p. Conclusion ATF2 and NEAT1 form a positive feedback loop mediated by miR-26a-5p and coordinately contribute to LUAD progression.

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