uc.338 targets p21 and cyclin D1 via PI3K/AKT pathway activation to promote cell proliferation in colorectal cancer

Zhang, Yue; Wang, Shijia; Qian, Wenwei; Ji, Dongjian; Wang, Qingyuan; Zhang, Zhiyuan; Wang, Sen; Ji, Bing; Fu, Zan; Sun, Yueming

doi:10.3892/or.2018.6480

Cited by 16 publications

(19 citation statements)

References 33 publications

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“…In addition, the data demonstrated that knockdown of CacyBP/SIP inhibited the cell cycle by inducing G 1 /S phase arrest. p21, also known as CDK inhibitor 1, is capable of binding and inhibiting numerous cyclin/CDK complexes, such as cyclin D/CKD4 (27), cyclin E/CDK2 (28) and cyclin A/CDK2 (29). The results of the present study demonstrated that knockdown of CacyBP/SIP protein was associated with an increase in p21 levels and decrease in CDK2, CDK4, cyclin D and cyclin E levels.…”

Section: Discussionsupporting

confidence: 56%

CacyBP/SIP promotes tumor progression by regulating apoptosis and arresting the cell cycle in osteosarcoma

Zhao

Zhang

et al. 2020

Exp Ther Med

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Osteosarcoma (OS) is the most common primary malignant bone tumor in pediatric and adolescent patients. The calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP) performs an essential function in cell proliferation and apoptosis. The present study investigated the effect of CacyBP/SIP in OS cell proliferation and apoptosis. CacyBP/SIP mRNA expression levels were evaluated in four OS cell lines by quantitative PCR. CacyBP/SIP expression was downregulated in Saos-2 cells using a lentivirus transfection system and the transfection efficiency was analyzed. The effects of CacyBP/SIP downregulation on Saos-2 cell proliferation and colony-formation ability were evaluated by MTT and colony-formation assays. The effect of CacyBP/SIP knockdown on Saos-2 cell cycle and apoptosis was analyzed by flow cytometry cell sorting. The Cancer Genome Atlas (TCGA) data was analyzed for validation. Human OS cell lines Saos-2, MG-63, HOS and U20S expressed CacyBP/SIP mRNA. CacyBP/SIP knockdown significantly inhibited cell proliferation and colony-formation ability. G 1 /S phase arrest was induced by CacyBP/SIP downregulation, which also resulted in the downregulation of CDK and cyclins and the upregulation of p21. In addition, CacyBP/SIP downregulation induced Saos-2 cell apoptosis mediated by Bax and Bcl-2. High expression of CacyBP/SIP was significantly associated with poor prognosis in TCGA sarcoma database. Thus, CacyBP/SIP performs important functions in the proliferation and apoptosis of human OS cells.

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Section: Discussionsupporting

confidence: 56%

CacyBP/SIP promotes tumor progression by regulating apoptosis and arresting the cell cycle in osteosarcoma

Zhao

Zhang

et al. 2020

Exp Ther Med

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“…p21, a cyclin-dependent kinase inhibitor, almost inhibits all cyclin/CDK complexes. The expression level of p21 and cyclin D1 can reflect the proliferation of MMCs (18). In this study, the results of western blot analysis revealed that transfection with miR-379-5p mimics attenuated the decrease and increase in the expression level of p21 and cyclin D1, respectively induced by HG stimulation (Fig.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA‑379‑5p suppresses renal fibrosis by regulating the LIN28/let‑7 axis in diabetic nephropathy

Wang

et al. 2019

Int J Mol Med

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MicroRNAs (miRNAs or miRs) play an important role in pathological processes in diabetic nephropathy (DN). This study aimed to explore whether miR-379-5p is associated with renal fibrosis in DN and to elucidate the underlying mechanisms. In vitro experiments indicated that miR-379-5p expression was downregulated by high glucose (HG) treatment in mouse mesangial cells (MMCs). Transfection with miR-379-5p mimics suppressed the proliferation and the accumulation of extracellular matrix (ECM) components, which were promoted by HG treatment. LIN28B was proven to be a direct target of miR-379-5p by luciferase report assay. In addition, the loss of expression of LIN28B, as well as the decrease in cell proliferation and in the accumulation of ECM components, which were induced by the knockdown of LIN28B, were attenuated in the MMCs following transfection with miR-379-5p inhibitors. Furthermore, type 2 diabetic db/db mice were used to examine the efficiency of miR-379-5p agomir in the alleviation of renal fibrosis. Consistent with the results of the in vitro experiments, miR-379-5p agomir suppressed mesangial cell proliferation and the accumulation of ECM components by regulating the LIN28B/let-7 pathway. Taken together, the findings of this study suggest that miR-379-5p is highly involved in renal fibrosis in DN, and that it may be a potential effective therapeutic target for DN.

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“…For instance, circGRAMD1B/miR-130a-3p axis negatively regulates PTEN and p21, allowing higher proliferation, migration and invasion rates of GC cells [62]. Curiously, p21 is a cyclin/cdk inhibitor protein directly associated with the PI3K/Akt pathway [88]. We also highlight the tumor suppressor miR-375 that decreases PDK1 activity in PI3K/Akt signaling [79].…”

Section: Discussionmentioning

confidence: 84%

The Biological Role of Sponge Circular RNAs in Gastric Cancer: Main Players or Coadjuvants?

Pereira

Magalhães

Pantoja

et al. 2020

Cancers

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Circular RNAs (circRNAs) are a new class of long noncoding RNAs able to perform multiple functions, including sponging microRNAs (miRNAs) and RNA-Binding Proteins (RBPs). They play an important role in gastric carcinogenesis, but its involvement during gastric cancer (GC) development and progression are not well understood. We gathered miRNA and/or RBPs sponge circRNAs present in GC, and accessed their biological roles through functional enrichment of their target genes or ligand RBPs. We identified 54 sponge circRNAs in GC that are able to sponge 51 miRNAs and 103 RBPs. Then, we evaluated their host gene expression using The Cancer Genome Atlas (TCGA) database and observed that COL1A2 is the most overexpressed gene, which may be due to circHIPK3/miR-29b-c/COL1A2 axis dysregulation. We identified 27 GC-related pathways that may be affected mainly by circPVT1, circHIPK3 and circNF1. Our results indicate that circHIPK3/miR-107/BDNF/LIN28 axis may mediate chemoresistance in GC, and that circPVT1, circHIPK3, circNF1, ciRS-7 and circ_0000096 appear to be involved in gastrointestinal cancer development. Lastly, circHIPK3, circNRIP1 and circSMARCA5 were identified in different ethnic populations and may be ubiquitous modulators of gastric carcinogenesis. Overall, the studied sponge circRNAs are part of a complex RBP-circRNA-miRNA-mRNA interaction network, and are involved in the establishment, chemoresistance and progression of GC.

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uc.338 targets p21 and cyclin D1 via PI3K/AKT pathway activation to promote cell proliferation in colorectal cancer

Cited by 16 publications

References 33 publications

CacyBP/SIP promotes tumor progression by regulating apoptosis and arresting the cell cycle in osteosarcoma

CacyBP/SIP promotes tumor progression by regulating apoptosis and arresting the cell cycle in osteosarcoma

MicroRNA‑379‑5p suppresses renal fibrosis by regulating the LIN28/let‑7 axis in diabetic nephropathy

The Biological Role of Sponge Circular RNAs in Gastric Cancer: Main Players or Coadjuvants?

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