Correction: RANBP1 promotes colorectal cancer progression by regulating pre-miRNA nuclear export via a positive feedback loop with YAP

BackgroundColorectal cancer (CRC) is a common malignant tumor with high metastatic and recurrent rates. This study probes the effect and mechanism of long non-coding RNA MIR31HG on the progression of CRC cells.Materials and MethodsQuantitative real-time PCR (qRT-PCR) was used to analyze the expression of MIR31HG and miR-361-3p in CRC tissues and normal tissues. Gain- or loss-of-function assays were conducted to examine the roles of MIR31HG, miR-361-3p and YY1 transcription factor (YY1) in the CRC progression. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and colony formation experiment were conducted to test CRC cell proliferation. CRC cell invasion was determined by Transwell assay. The glucose detection kit and lactic acid detection kit were utilized to monitor the levels of glucose and lactate in CRC cells. The glycolysis level in CRC cells was examined by the glycolytic stress experiment. Western blot was performed to compare the expression of glycolysis-related proteins (PKM2, GLUT1 and HK2) and angiogenesis-related proteins (including VEGFA, ANGPT1, HIF1A and TIMP1) in HUVECs. The binding relationships between MIR31HG and miR-361-3p, miR-361-3p and YY1 were evaluated by the dual-luciferase reporter assay and RNA immunoprecipitation (RIP).ResultsMIR31HG was up-regulated in CRC tissues and was associated with poorer prognosis of CRC patients. The in-vitro and in-vivo experiments confirmed that overexpressing MIR31HG heightened the proliferation, growth, invasion, glycolysis and lung metastasis of CRC cells as well as the angiogenesis of HUVECs. In addition, MIR3HG overexpression promoted YY1 mRNA and protein level, and forced overexpression of YY1 enhanced MIR31HG level. Overexpressing YY1 reversed the tumor-suppressive effect mediated by MIR31HG knockdown. miR-361-3p, which was inhibited by MIR31HG overexpression, repressed the malignant behaviors of CRC cells. miR-361-3p-mediated anti-tumor effects were mostly reversed by upregulating MIR31HG. Further mechanism studies illustrated that miR-361-3p targeted and negatively regulated the expression of YY1.ConclusionThis study reveals that MIR31HG functions as an oncogenic gene in CRC via forming a positive feedback loop of MIR31HG-miR-361-3p-YY1.

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A FoxM1/lncRNA PTTG3P/YAP1 Positive Feedback Loop Controls Colorectal Cancer Progression

10.21203/rs.3.rs-587835/v1 ◽

2021 ◽

Author(s):

Yang zheng ◽

Guilin yu ◽

Yiyang Liu ◽

Longfei Xie ◽

Jinnian Ge ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Positive Feedback ◽

Promoter Region ◽

Feedback Loop ◽

Ectopic Expression ◽

Luciferase Assay ◽

Mice Model ◽

Positive Feedback Loop ◽

Dismal Prognosis

Abstract Background Pseudogenes are vital regulators of cancer progression. PTTG3P biological function in colorectal cancer (CRC) needs further to be clarified. Methods qRT-PCR was adopted to measure the PTTG3P expression. Functional studies were examined by CCK-8, glucose uptake, lactate assay, ATP assay, ECAR assay and xenograft mice model. The mechanism of PTTG3P was carried by GSEA. Chromatin immunoprecipitation (ChIP) and luciferase assay were explored to certify the binding activity between PTTG3P promoter region and FoxM1. Results Ectopic expression of PTTG3P was involved in CRC and related to dismal prognosis. Experimental evidence discovered that PTTG3P enhanced cell proliferation and glycolysis through YAP1 and regulated FoxM1(Hippo pathway target gene). Further, LDHA knockdown or glycolysis inhibitor (2-DG,3-BG) recovered PTTG3P-induced proliferation. Mechanically, FoxM1 increase PTTG3P expression at transcription level and the PTTG3P promoter region of -900 to -1200 nt is necessary for binding with FoxM1, thus forming a positive feedback loop to facilitates the CRC progression. Additionally, FoxM1 depletion could rescue the PTTG3P function. Conclusions A FoxM1/lncRNA PTTG3P/YAP1 positive feedback loop plays a vital part in CRC progression, and targeting FoxM1, PTTG3P and YAP1 provides therapeutic targets for CRC treatment.

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