Long noncoding RNAs (lncRNAs) play important roles in regulating the development and progression of many cancers. However, the clinical significance of specific lncRNAs in the context of nasopharyngeal carcinoma (NPC) and the molecular mechanisms by which they regulate this form of cancer remain largely unclear. In this study we found that the lncRNA PVT1 was upregulated in NPC, and that in patients this upregulation was associated with reduced survival. RNA sequencing revealed that PVT1 was responsible for regulating NPC cell proliferation and for controlling a hypoxia-related phenotype in these cells. PVT1 knockdown reduced NPC cell proliferation, colony formation, and tumorigenesis in a subcutaneous mouse xenograft model systems. We further found that PVT1 serves as a scaffold for the chromatin modification factor KAT2A, which mediates histone 3 lysine 9 acetylation (H3K9), recruiting the nuclear receptor binding protein TIF1β to activate NF90 transcription, thereby increasing HIF-1α stability and promoting a malignant phenotype in NPC cells. Overexpression of NF90 or HIF-1α restored the proliferation in cells that had ceased proliferating due to PVT1 or KAT2A depletion. Conversely, overexpression of active KAT2A or TIF1β, but not of KAT2A acetyltransferase activity-deficient mutants or TIF1β isoforms lacking H3K9ac binding sites, promoted a PVT1-mediated increase in NF90 transcription, as well as increased HIF-1α stability and cell proliferation. PVT1 knockdown enhanced the radiosensitization effect in NPC cells via inhibiting binding between H3K9ac and TIF1β in a manner. Taken together, our results demonstrate that PVT1 serves an oncogenic role and plays an important role in radiosensitivity in malignant NPC via activating the KAT2A acetyltransferase and stabilizing HIF-1α.

/pdf/the-lncrna-pvt1-regulates-nasopharyngeal-carcinoma-cell-3q7sq1wnin.pdf

The lncRNA PVT1 regulates nasopharyngeal carcinoma cell proliferation via activating the KAT2A acetyltransferase and stabilizing HIF-1α.

Research of the past view years expanded our understanding of the various physiological functions the cell-fate determining transcription factor SOX2 exerts in ontogenesis, reprogramming, and cancer. However, while scientific reports featuring novel and exciting aspects of SOX2-driven biology are published in near weekly routine, investigations in the underlying protein-biochemical processes that transiently tailor SOX2 activity to situational demand are underrepresented and have not yet been comprehensively summarized. Largely unrecognizable to modern array or sequencing-based technology, various protein secondary modifications and concomitant function modulations have been reported for SOX2. The chemical modifications imposed onto SOX2 are inherently heterogeneous, comprising singular or clustered events of phosphorylation, methylation, acetylation, ubiquitination, SUMOylation, PARPylation, and O-glycosylation that reciprocally affect each other and critically impact SOX2 functionality, often in a tissue and species-specific manner. One recurring regulatory principle though is the canonical PI3K/AKT signaling axis to which SOX2 relates in various entangled, albeit not exclusive ways. Here we provide a comprehensive review of the current knowledge on SOX2 protein modifications, their proposed relationship to the PI3K/AKT pathway, and regulatory influence on SOX2 with regards to stemness, reprogramming, and cancer.

/pdf/sox2-protein-biochemistry-in-stemness-reprogramming-and-dhskbbq139.pdf

SOX2 protein biochemistry in stemness, reprogramming, and cancer: the PI3K/AKT/SOX2 axis and beyond.

Conventional therapies and novel molecular targeted therapies against breast cancer have gained great advances over the past two decades. However, poor prognosis and low survival rate are far from expectation for improvement, particularly in patients with triple negative breast cancer (TNBC). Here, we found that lncRNA DANCR was significantly overregulated in TNBC tissues and cell lines compared with normal breast tissues or other type of breast cancer. Knockdown of DANCR suppressed TNBC proliferation both in vitro and in vivo. Further study of underlying mechanisms demonstrated that DANCR bound with RXRA and increased its serine 49/78 phosphorylation via GSK3β, resulting in activating PIK3CA transcription, and subsequently enhanced PI3K/AKT signaling and TNBC tumorigenesis. Taken together, Our findings identified DANCR as an pro-oncogene and uncoverd a new working pattern of lncRNA to mediate TNBC tumorigenesis, which may be a potential therapeutic target for improving treatment of TNBC.

/pdf/lncrna-dancr-upregulates-pi3k-akt-signaling-through-5731gro6i5.pdf

LncRNA DANCR upregulates PI3K/AKT signaling through activating serine phosphorylation of RXRA.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. This study aims to understand the underlying mechanism of lncRNA, actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1) in mediating chemotherapeutic resistance in NSCLC. The levels of AFAP1-AS1 in NSCLC tissues and cells were determined using RT-PCR. The protein levels of RRM2, EGFR, and p-AKT were analyzed using Western blotting. Binding between AFAP1-AS1 and miR-139-5p was confirmed using dual luciferase reporter and RNA immunoprecipitation (RIP) assays, and binding between miR-139-5p and RRM2 was confirmed by a dual luciferase reporter assay. NSCLC cell proliferation, apoptosis, and colony formation were examined using MTT, flow cytometry, and colony formation assays, respectively. It was found that AFAP1-AS1 expression was upregulated in NSCLC tissues and cells. In addition, AFAP1-AS1 bound to and downregulated the expression of miR-139-5p, which was reduced in NSCLC tissues. Knockdown of AFAP1-AS1 and overexpression of miR-139-5p inhibited NSCLC cell proliferation, colony formation and chemotherapy resistance and increased cell apoptosis. Additionally, AFAP1-AS1 upregulates RRM2 expression via sponging miR-139-5p. Furthermore, AFAP1-AS1 enhanced NSCLC cell proliferation and chemotherapy resistance through upregulation of RRM2 by inhibiting miR-139-5p expression. Moreover, RRM2 promoted cellular chemotherapy resistance by activating EGFR/AKT. Finally, knockdown of AFAP1-AS1 significantly suppressed tumor growth and chemoresistance in nude mice. In conclusion, AFAP1-AS1 promoted chemotherapy resistance by supressing miR-139-5p expression and promoting RRM2/EGFR/AKT signaling pathway in NSCLC cells.

/pdf/lncrna-afap1-as1-supresses-mir-139-5p-and-promotes-cell-39tnh2bzmc.pdf

LncRNA AFAP1-AS1 Supresses miR-139-5p and Promotes Cell Proliferation and Chemotherapy Resistance of Non-small Cell Lung Cancer by Competitively Upregulating RRM2

Acute renal injury (AKI) causes a long-term risk for progressing into chronic kidney disease (CKD) and interstitial fibrosis. Yes-associated protein (YAP), a key transcriptional cofactor in Hippo signaling pathway, shuttles between the cytoplasm and nucleus, which is required for the renal tubular epithelial cells repair in the acute phase of AKI. In this study we investigated the role of YAP during ischemia-reperfusion (IR)-induced AKI to CKD. Mice were subjected to left kidney IR followed by removal of the right kidney on the day before tissue harvests. Mouse shRNA expression adenovirus (Ad-shYAP or Ad-shKLF4) and mouse KLF4 expression adenovirus (Ad-KLF4) were delivered to mice by intrarenal injection on D7 after IR. We showed that the expression and nucleus distribution of YAP were persistently increased until the end of experiment (D21 after IR). The sustained activation of YAP in post-acute phase of AKI was accompanied by renal dysfunction and interstitial fibrosis. Knockdown of YAP significantly attenuated IR-induced renal dysfunction and decreased the expression of fibrogenic factors TGF-β and CTGF in the kidney. We showed that the expression of the transcription factor KLF4, lined on the upstream of YAP, was also persistently increased. Knockdown on KLF4 attenuated YAP increase and nuclear translocation as well as renal functional deterioration and interstitial fibrosis in IR mice, whereas KLF4 overexpression caused opposite effects. KLF4 increased the expression of ITCH, and ITCH facilitated YAP nuclear translocation via degrading LATS1. Furthermore, we demonstrated in primary cultured renal tubular cells that KLF4 bound to the promoter region of YAP and positively regulates YAP expression. In biopsy sample from CKD patients, we also observed increased expression and nuclear distribution of YAP. In conclusion, the activation of YAP in the post-acute phase of AKI is implicated in renal functional deterioration and fibrosis although it exhibits beneficial effect in acute phase. Reprogramming factor KLF4 is responsible for the persistent activation of YAP. Blocking the activation of KLF4-YAP pathway might be a way to prevent the transition of AKI into CKD.

KLF4 initiates sustained YAP activation to promote renal fibrosis in mice after ischemia-reperfusion kidney injury.

Increasing evidences have shown that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. However, the contributions of lncRNAs to colorectal cancer remain largely unknown. Here, we identify a lncRNA AFAP1-AS1 that facilitates colorectal cancer, where it is upregulated. AFAP1-AS1 expression was associated with colorectal cancer patient survival. AFAP1-AS1 knockdown inhibited cell proliferation, cell cycle, and tumorigenesis in an subcutaneous mouse xenograft model system. Further data demonstrated that AFAP1-AS1 was associated with enhancer of zeste homolog 2 (EZH2) and that this association was required for the repression of EZH2 target genes. Our findings indicate that AFAP1-AS1 is an oncogenic lncRNA that promotes tumor progression and may be a novel prognostic factor in colorectal cancer. Targeting AFAP1-AS1 might be a potential therapeutic strategy for colorectal cancer treatment.

Long noncoding RNA AFAP1-AS1 facilitates tumor growth through enhancer of zeste homolog 2 in colorectal cancer.

SOX2 is a transcription factor that contributes to transcription modification and cancer, but the mechanism by which SOX2 regulates nasopharyngeal carcinoma cell proliferation is not well understood. Here, we identify a SOX2 signaling pathway that facilitates nasopharyngeal carcinoma, where it is upregulated. SOX2 expression was associated with nasopharyngeal carcinoma patient survival. SOX2 knockdown inhibited cell proliferation, colony formation, and tumorigenesis in an subcutaneous mouse xenograft model system. Six hundred and ninety-nine candidate SOX2 downstream dysregulated genes were identified in nasopharyngeal carcinoma cells through cDNA microarray analysis. SOX2 recruited the nuclear transcription factor KLF4 to bind to the PIK3CA promoter upregulate PIK3CA expression, acting to enhance PI3K/AKT signaling and tumorigenesis by upregulating PIK3CA expression. Besides, overexpressing activated AKT or PIK3CA rescued the growth inhibition of cells due to SOX2 knockdown. Together, our study suggest that SOX2 exhibits oncogenic properties and may be a reliable molecular biomarker in nasopharyngeal carcinoma. Targeting SOX2 might be a promising treatment strategy for nasopharyngeal carcinoma treatment.

/pdf/sox2-recruits-klf4-to-regulate-nasopharyngeal-carcinoma-46x4tns600.pdf

SOX2 recruits KLF4 to regulate nasopharyngeal carcinoma proliferation via PI3K/AKT signaling

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Haiyan Chen

Author Tools

Chat about Author

Papers

Long noncoding RNA AFAP1-AS1 facilitates tumor growth through enhancer of zeste homolog 2 in colorectal cancer.

SOX2 recruits KLF4 to regulate nasopharyngeal carcinoma proliferation via PI3K/AKT signaling