&lt;p&gt;FNDC3B, Targeted by miR-125a-5p and miR-217, Promotes the Proliferation and Invasion of Colorectal Cancer Cells via PI3K/mTOR Signaling&lt;/p&gt;

Clinical Laboratory Analysis

Peng

Jiang

et al. 2022

Background Circular RNAs (circRNAs) are closely associated with the progression of oral squamous cell carcinoma (OSCC). circRNA_0001971 has been proved to accelerate the OSCC development. Here, we aim to identify the new molecular mechanism of hsa_circRNA_0001971 (circRNA_0001971) in OSCC. Methods The levels of circRNA_0001971, miR‐186‐5p, and fibronectin type III domain containing 3B (FNDC3B) in tissues and cells were verified by qRT‐PCR or Western blotting. The interaction between circRNA_0001971, miR‐186‐5p, and FNDC3B was identified by bioinformatics analysis, luciferase assay, and RIP assay. The effect of circRNA_0001971/miR‐186‐5p/FNDC3B axis on OSCC cell proliferation, migration, and invasion by cell functional experiments including CCK8, wound healing, and transwell assays. Results Our study displayed that circRNA_0001971 and FNDC3B were elevated in OSCC, whereas miR‐186‐5p was declined in OSCC. Silencing circRNA_0001971 attenuated the malignancy of OSCC cells by suppressing proliferation, migration, and invasion. In OSCC cells, circRNA_0001971 sponged miR‐186‐5p to enhance FNDC3B. Due to the interaction between circRNA_0001971, miR‐186‐5p, and FNDC3B, FNDC3B overexpression relieved the negative function of silencing circRNA_0001971 in OSCC cells. Conclusion Overall, our study discovered that circRNA_0001971 was a tumor promoter in OSCC progression by targeting miR‐186‐5p/FNDC3B axis.

Section: Discussionmentioning

confidence: 99%

Hsa_circRNA_0001971 contributes to oral squamous cell carcinoma progression via miR‐186‐5p/Fibronectin type III domain containing 3B axis

Clinical Laboratory Analysis

Peng

Jiang

et al. 2022

“…Integrin β3 promotes cardiomyocyte proliferation and attenuates hypoxia‐induced apoptosis via regulating the PTEN/Akt/mTOR pathway (Wei et al, 2020). FNDC3B facilitated cell proliferation and invasion via PI3K/mTOR signaling and further promoted CRC progression (Li et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…FNDC3B facilitated cell proliferation and invasion via PI3K/mTOR signaling and further promoted CRC progression (Li et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

PSPH induces cell autophagy and promotes cell proliferation and invasion in the hepatocellular carcinoma cell line Huh7 via the AMPK/mTOR/ULK1 signaling pathway

Wang²,

Cell Biology International

et al. 2020

Phosphoserine phosphatase (PSPH), a key enzyme of the l‐serine synthesis pathway, has been involved in cancer progression and survival. However, limited evidence revealed the PSPH influence on hepatocellular carcinoma (HCC). Herein, we observed that PSPH expression was upregulated in both HCC tissues and cell lines, which was determined by western blotting. TCGA database showed that the PSPH protein levels were significantly upregulated and affected patient survival rates in HCC. Then gain‐ and loss‐of‐function manipulations were performed by transfection with a pcDNA‐PSPH expression vector or a specific short interfering RNA against PSPH in Huh7 cells. Huh7 cell proliferation, stemness, invasion, and apoptosis were assessed by using CCK‐8 test, colony formation assay, Transwell assay, and Flow cytometry analysis, respectively, and levels of autophagy‐related proteins were detected by using western blotting. The results showed that PSPH could induce Huh7 cell autophagy, promote cell proliferation and invasion, and inhibit apoptosis. The knockdown of PSPH could inhibit Huh7 cell proliferation, invasion, and autophagy. Furthermore, PSPH activated Liver kinase B1 (LKB1) and TGF beta‐activated kinase 1 (TAK1), affected the adenosine 5′‐monophosphate‐activated protein kinase (AMPK)/mTOR/ULK1 signaling pathway, but could not activate calcium/calmodulin‐dependent protein kinase kinase (CaMKK) in Huh7 cells. Inhibition of either LKB1, TAK1, or AMPK could eliminate the effect of PSPH overexpression on Huh7 cell behaviors. However, inhibition of CaMKK could not influence the effect of PSPH overexpression on Huh7 cell behaviors. In conclusion, PSPH could induce autophagy, promote proliferation and invasion, and inhibit apoptosis in HCC cells via the AMPK/mTOR/ULK1 signaling pathway.

“…Tetraspanins act as scaffolds forming membrane microdomains that mediate adhesion, signaling, fusion and fission, and CD151 is well known for its role in integrin signaling [53]. Candidate FNDC3B contains a fibronectin type III domain involved in interactions with integrins and knockdown of this genes in HCT8 leads to a decrease in phosphorylation of PI3K [54]. Polymerization of host actin is a prominent feature of Cryptosporidium invasion and host modification and there is evidence for parasite engagement of host integrins and PI3K signaling [55,56] in this context.…”

Section: Parasite Attachment and Invasionmentioning

confidence: 99%

A genetic screen identifies a protective type III interferon response toCryptosporidiumthat requires TLR3 dependent recognition

Gibson

Sateriale

Dumaine

et al. 2021

Preprint

Cryptosporidium is a leading cause of severe diarrhea and diarrheal-related death in children worldwide. As an obligate intracellular parasite, Cryptosporidium relies on intestinal epithelial cells to provide a niche for its growth and survival, but little is known about the contributions that the infected cell makes to this relationship. Here we conducted a genome wide CRISPR/Cas9 knockout screen to discover host genes required for Cryptosporidium parvum infection and/or host cell survival. Gene enrichment analysis indicated that the host interferon response, glycosaminoglycan (GAG) and glycosylphosphatidylinositol (GPI) anchor biosynthesis are important determinants of susceptibility to C. parvum infection. Several of these pathways are linked to parasite attachment and invasion and C-type lectins on the surface of the parasite. Evaluation of transcript and protein induction of innate interferons revealed a pronounced type III interferon response to Cryptosporidium in human cells as well as in mice. Treatment of mice with IFNλ reduced infection burden and protected immunocompromised mice from severe outcomes including death, with effects that required STAT1 signaling in the enterocyte. Initiation of this type III interferon response was dependent on sustained intracellular growth and mediated by the pattern recognition receptor TLR3. We conclude that host cell intrinsic recognition of Cryptosporidium results in IFNλ production critical to early protection against this infection.Author SummaryCryptosporidium infection is an important contributor to global childhood mortality. There are currently no vaccines available, and the only drug has limited efficacy in immunocompromised individuals and malnourished children who need it most. To discover which host proteins are essential for Cryptosporidium infection, we conducted a genome wide knockout screen in human host cells. Our results confirm the importance of glycosaminoglycans on the surface of epithelial cells for attachment and invasion of the parasite. We also found that host GPI anchor biosynthesis and interferon signaling pathways were enriched by our screen. Examining the role of interferon signaling further we found a type III interferon response, IFNλ, was generated in response to infection and shown to be initiated in the infected cell. Utilizing mouse models of infection, we found that the type III interferon response was important early during infection with its induction likely preceding IFNγ, a key cytokine for the control of this infection. We also determined that TLR3 was the pattern recognition receptor responsible for IFNλ production during Cryptosporidium infection. Our work shows that IFNλ acts directly on the enterocyte and its use in treating immunocompromised mice produced striking reductions in infection.