scholarly journals Variable roles of interleukin-17F in different cancers

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Tiina Mikkola ◽  
Rabeia Almahmoudi ◽  
Tuula Salo ◽  
Ahmed Al-Samadi
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Molecular Form ◽  
Vasculogenic Mimicry ◽  
Protective Role ◽  
Migration And Invasion ◽  
Cancer Type ◽  
Ovid Medline ◽  
Interleukin 17A ◽  
Inhibition Of Angiogenesis

Abstract Background Interleukin (IL)-17 family is a group of six cytokines that plays a central role in inflammatory processes and participates in cancer progression. Interleukin-17A has been shown to have mainly a protumorigenic role, but the other members of the IL-17 family, including IL-17F, have received less attention. Methods We applied systematic review guidelines to study the role of IL-17F, protein and mRNA expression, polymorphisms, and functions, in cancer. We carried out a systematic search in PubMed, Ovid Medline, Scopus, and Cochrane libraries, yielding 79 articles that met the inclusion criteria. Results The findings indicated that IL-17F has both anti- and protumorigenic roles, which depend on cancer type and the molecular form and location of IL-17F. As an example, the presence of IL-17F protein in tumor tissue and patient serum has a protective role in oral and pancreatic cancers, whereas it is protumorigenic in prostate and bladder cancers. These effects are proposed to be based on multiple mechanisms, such as inhibition of angiogenesis, vasculogenic mimicry and cancer cell proliferation, migration and invasion, and aggravating the inflammatory process. No solid evidence emerged for the correlation between IL-17F polymorphisms and cancer incidence or patients’ prognosis. Conclusion IL-17F is a multifaceted cytokine. There is a clear demand for more well-designed studies of IL-17F to elucidate its molecular mechanisms in different types of cancer. The studies presented in this article examined a variety of different designs, study populations and primary/secondary outcomes, which unfortunately reduces the value of direct interstudy comparisons.

scholarly journals TEAD4 modulated LncRNA MNX1-AS1 contributes to gastric cancer progression partly through suppressing BTG2 and activating BCL2

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
You Shuai ◽  
Zhonghua Ma ◽  
Weitao Liu ◽  
Tao Yu ◽  
Changsheng Yan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Mechanistic Model ◽  
Ectopic Expression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Tissue Samples ◽  
Reporter Assays

Abstract Background Gastric cancer (GC) is the third leading cause of cancer-related mortality globally. Long noncoding RNAs (lncRNAs) are dysregulated in obvious malignancies including GC and exploring the regulatory mechanisms underlying their expression is an attractive research area. However, these molecular mechanisms require further clarification, especially upstream mechanisms. Methods LncRNA MNX1-AS1 expression in GC tissue samples was investigated via microarray analysis and further determined in a cohort of GC tissues via quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Cell proliferation and flow cytometry assays were performed to confirm the roles of MNX1-AS1 in GC proliferation, cell cycle regulation, and apoptosis. The influence of MNX1-AS1 on GC cell migration and invasion was explored with Transwell assays. A xenograft tumour model was established to verify the effects of MNX1-AS1 on in vivo tumourigenesis. The TEAD4-involved upstream regulatory mechanism of MNX1-AS1 was explored through ChIP and luciferase reporter assays. The mechanistic model of MNX1-AS1 in regulating gene expression was further detected by subcellular fractionation, FISH, RIP, ChIP and luciferase reporter assays. Results It was found that MNX1-AS1 displayed obvious upregulation in GC tissue samples and cell lines, and ectopic expression of MNX1-AS1 predicted poor clinical outcomes for patients with GC. Overexpressed MNX1-AS1 expression promoted proliferation, migration and invasion of GC cells markedly, whereas decreased MNX1-AS1 expression elicited the opposite effects. Consistent with the in vitro results, MNX1-AS1 depletion effectively inhibited the growth of xenograft tumour in vivo. Mechanistically, TEAD4 directly bound the promoter region of MNX1-AS1 and stimulated the transcription of MNX1-AS1. Furthermore, MNX1-AS1 can sponge miR-6785-5p to upregulate the expression of BCL2 in GC cells. Meanwhile, MNX1-AS1 suppressed the transcription of BTG2 by recruiting polycomb repressive complex 2 to BTG2 promoter regions. Conclusions Our findings demonstrate that MNX1-AS1 may be able to serve as a prognostic indicator in GC patients and that TEAD4-activatd MNX1-AS1 can promote GC progression through EZH2/BTG2 and miR-6785-5p/BCL2 axes, implicating it as a novel and potent target for the treatment of GC.

scholarly journals Wnt5a Signaling in Normal and Cancer Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Yan Zhou ◽  
Thomas J. Kipps ◽  
Suping Zhang
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Target Cells ◽  
Dependent Manner ◽  
Self Renewal ◽  
Surface Receptors ◽  
Canonical Wnt

Wnt5a is involved in activating several noncanonical Wnt signaling pathways, which can inhibit or activate canonical Wnt/β-catenin signaling pathway in a receptor context-dependent manner. Wnt5a signaling is critical for regulating normal developmental processes, including stem cell self-renewal, proliferation, differentiation, migration, adhesion, and polarity. Moreover, the aberrant activation or inhibition of Wnt5a signaling is emerging as an important event in cancer progression, exerting both oncogenic and tumor suppressive effects. Recent studies show the involvement of Wnt5a signaling in regulating normal and cancer stem cell self-renewal, cancer cell proliferation, migration, and invasion. In this article, we review recent findings regarding the molecular mechanisms and roles of Wnt5a signaling in stem cells in embryogenesis and in the normal or neoplastic breast or ovary, highlighting that Wnt5a may have different effects on target cells depending on the surface receptors expressed by the target cell.

scholarly journals Cooperation of SRPK2, Numb and p53 in the malignant biology and chemosensitivity of colorectal cancer

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Guosen Wang ◽  
Weiwei Sheng ◽  
Jingtong Tang ◽  
Xin Li ◽  
Jianping Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Chemical Agent ◽  
Cell Migration And Invasion ◽  
Agent Treatment ◽  
Hct116 Cells

Abstract Serine-arginine protein kinase 2 (SRPK2) is aberrantly expressed in human malignancies including colorectal cancer (CRC). However, little is known about the molecular mechanisms, and the role of SRPK2 in chemosensitivity remains unexplored in CRC. We recently showed that SRPK2 promotes pancreatic cancer progression by down-regulating Numb and p53. Therefore, we investigated the cooperation between SRPK2, Numb and p53 in the cell migration, invasion and chemosensitivity of CRC in vitro. Here, we showed that SRPK2 expression was higher in CRC tumors than in nontumor tissues. SRPK2 expression was positively associated with clinicopathological characteristics of CRC patients, including tumor differentiation, T stage, N stage and UICC stage. Additionally, SRPK2 had no association with mutant p53 (mtp53) in SW480 and SW620 cells, but negatively regulated Numb and wild-type p53 (wtp53) in response to 5-fluorouracil or cisplatin treatment in HCT116 cells. Moreover, SRPK2, Numb and p53 coimmunoprecipitated into a triple complex with or without the treatment of 5-fluorouracil in HCT116 cells, and p53 knockdown reversed the up-regulation of wtp53 induced by SRPK2 silencing with chemical agent treatment. Furthermore, overexpression of SRPK2 increased cell migration and invasion and decreased chemosensitivity to 5-fluorouracil or cisplatin in HCT116 cells. Conversely, SRPK2 silencing decreased cell migration and invasion and increased chemosensitivity to 5-fluorouracil or cisplatin, yet these effects could be reversed by p53 knockdown under chemical agent treatment. These results thus reveal a novel role of SRPK2-Numb-p53 signaling in the progression of CRC and demonstrate that SRPK2 is a potential therapeutic target for CRC clinical therapy.

Molecular Regulatory Roles of Long Non-coding RNA HOTTIP: An Overview in Gastrointestinal Cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Ummi Zulaiqha Hamid ◽  
Maw Shin Sim ◽  
Rhanye Mac Guad ◽  
Vetriselvan Subramaniyan ◽  
Mahendran Sekar ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Diagnostic Value ◽  
Migration And Invasion ◽  
Cellular Functions ◽  
Poor Overall Survival ◽  
Gi Cancer ◽  
Non Coding Rna ◽  
Gi Cancers ◽  
Cancer Phenotypes

: Gastrointestinal (GI) cancers presented an alarmingly high number of new cancer cases worldwide and highly characterised with poor prognosis. The poor overall survival is mainly due to late detection and emerging challenges in treatment, particularly chemoresistance. Thus, the identification of novel molecular targets in GI cancer is highly regarded as the main focus. Recently, long non-coding RNAs (lncRNAs) have been discovered as a potential novel molecular target for combating cancer, as it is highly associated with carcinogenesis and has a great impact on cancer progression. Amongst lncRNAs, HOTIIP has demonstrated a prominent oncogenic regulation in cancer progression, particularly in GI cancers, including oesophageal cancer, gastric cancer, hepatocellular carcinoma, pancreatic cancer and colorectal cancer. This review aimed to present a focused update on the regulatory roles of HOTTIP in GI cancer progression and chemoresistance, as well as deciphering the associated molecular mechanisms underlying their impact on cancer phenotypes and chemoresistance and the key molecules involved. It has been reported that it regulates the expression of various genes and proteins in GI cancers that impacts on the cellular functions, including proliferation, adhesion, migration and invasion, apoptosis, chemosensitivity and tumour differentiation. Furthermore, HOTTIP was also discovered to have a higher diagnostic value as compared to existing diagnostic biomarkers. In overall, HOTTIP has presented itself as a novel therapeutic target and potential diagnostic biomarker in the development of GI cancer treatment.

scholarly journals The polypeptide GALNT6 Displays Redundant Functions upon Suppression of its Closest Homolog GALNT3 in Mediating Aberrant O-Glycosylation, Associated with Ovarian Cancer Progression

2019 ◽  
Vol 20 (9) ◽  
pp. 2264 ◽  
Author(s):  
Razan Sheta ◽  
Magdalena Bachvarova ◽  
Elizabeth Macdonald ◽  
Stephane Gobeil ◽  
Barbara Vanderhyden ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Survival Rates ◽  
Functional Redundancy ◽  
Tumor Formation ◽  
Migration And Invasion ◽  
Gene Ablation

Epithelial ovarian cancer (EOC) represents the most lethal gynecologic malignancy; a better understanding of the molecular mechanisms associated with EOC etiology could substantially improve EOC management. Aberrant O-glycosylation in cancer is attributed to alteration of N-acetylgalactosaminyltransferases (GalNAc-Ts). Reports suggest a genetic and functional redundancy between GalNAc-Ts, and our previous data are indicative of an induction of GALNT6 expression upon GALNT3 suppression in EOC cells. We performed single GALNT3 and double GALNT3/T6 suppression in EOC cells, using a combination of the CRISPR-Cas9 system and shRNA-mediated gene silencing. The effect of single GALNT3 and double GALNT3/T6 inhibition was monitored both in vitro (on EOC cells roliferation, migration, and invasion) and in vivo (on tumor formation and survival of experimental animals). We confirmed that GALNT3 gene ablation leads to strong and rather compensatory GALNT6 upregulation in EOC cells. Moreover, double GALNT3/T6 suppression was significantly associated with stronger inhibitory effects on EOC cell proliferation, migration, and invasion, and accordingly displayed a significant increase in animal survival rates compared with GALNT3-ablated and control (Ctrl) EOC cells. Our data suggest a possible functional redundancy of GalNAc-Ts (GALNT3 and T6) in EOC, with the perspective of using both these enzymes as novel EOC biomarkers and/or therapeutic targets.

scholarly journals Long noncoding RNA CASC2c inhibited cell proliferation in hepatocellular carcinoma by inactivated ERK1/2 and Wnt/β-catenin signaling pathway

2019 ◽  
Vol 22 (3) ◽  
pp. 302-310 ◽  
Author(s):  
Q. Y. Li ◽  
K. Yang ◽  
F. G. Liu ◽  
X. G. Sun ◽  
L. Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Cancer Susceptibility ◽  
Vital Role ◽  
Migration And Invasion ◽  
Tumor Tissues ◽  
Hcc Cells

Abstract Purpose Long non-coding RNAs (lncRNAs) have been shown to play important roles in tumorigenesis, but their biological functions and the underlying molecular mechanisms remain unclear. Alternative splicing of five exons results in three transcript variants of cancer susceptibility 2 (CASC2): the lncRNAs CASC2a, CASC2b, and CASC2c. CASC2a/b have been found to have crucial regulatory functions in a number of malignancies, but few studies have examined the effects of CASC2c in cancers. The objective of the study was to investigate the role of CASC2c in the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells. Methods This study first investigated the expression levels of CASC2c in tumor tissues, corresponding non-tumor tissues and cells using quantitative real-time polymerase chain reaction. The function and underlying molecular mechanism of CASC2c in human HCC were investigated in QGY-7703 cell line, as well as in gastric cancer (GC) cell and colorectal cancer (CRC) cell. Results In the present work, we observed that CASC2c was significantly down-regulated in HCC tissues and cells. Moreover, its overexpression remarkably inhibited the growth, migration, and invasion of HCC cells in vitro and promoted their apoptosis. Furthermore, we demonstrated that CASC2c overexpression decreased p-ERK1/2 levels in HCC, GC, and CRC cells. Interestingly, while overexpression of CASC2c decreased β-catenin expression in HCC and GC cells, it increased that in CRC cells. Conclusion The lncRNA–CASC2c has a vital role in tumorigenesis and cancer progression, and may serve as a biomarker or therapeutic target in cancer treatment via down-regulation of the ERK1/2 and Wnt/β-catenin signaling pathways.

scholarly journals Silencing of lncRNA MIR497HG via CRISPR/Cas13d Induces Bladder Cancer Progression Through Promoting the Crosstalk Between Hippo/Yap and TGF-β/Smad Signaling

2020 ◽  
Vol 7 ◽  
Author(s):  
Changshui Zhuang ◽  
Ying Liu ◽  
Shengqiang Fu ◽  
Chaobo Yuan ◽  
Jingwen Luo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Line ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Pathological Process ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion

A subset of long non-coding RNAs (lncRNAs), categorized as miRNA-host gene lncRNAs (lnc-miRHGs), is processed to produce miRNAs and involved in cancer progression. This work aimed to investigate the influences and the molecular mechanisms of lnc-miRHGs MIR497HG in bladder cancer (BCa). The miR-497 and miR-195 were derived from MIR497HG. We identified that lnc-miRHG MIR497HG and two harbored miRNAs, miR-497 and miR-195, were downregulated in BCa by analyzing The Cancer Genome Atlas and our dataset. Silencing of MIR497HG by CRISPR/Cas13d in BCa cell line 5637 promoted cell growth, migration, and invasion in vitro. Conversely, overexpression of MIR497HG suppressed cell progression in BCa cell line T24. MiR-497/miR-195 mimics rescued significantly the oncogenic roles of knockdown of MIR497HG by CRISPR/Cas13d in BCa. Mechanistically, miR-497 and miR-195 co-ordinately suppressed multiple key components in Hippo/Yap and transforming growth factor β signaling and particularly attenuated the interaction between Yap and Smad3. In addition, E2F4 was proven to be critical for silencing MIR497HG transcription in BCa cells. In short, we propose for the first time to reveal the function and mechanisms of MIR497HG in BCa. Blocking the pathological process may be a potential strategy for the treatment of BCa.

scholarly journals High TRAF6 Expression Is Associated With Esophageal Carcinoma Recurrence and Prompts Cancer Cell Invasion

2017 ◽  
Vol 25 (4) ◽  
pp. 485-493 ◽  
Author(s):  
Xinyang Liu ◽  
Zhichao Wang ◽  
Guoliang Zhang ◽  
Qikun Zhu ◽  
Hui Zeng ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Molecular Mechanisms ◽  
Tumor Necrosis Factor Receptor ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Underlying Mechanisms ◽  
Patient Prognosis ◽  
Cancer Tissues

Esophageal cancer is one of the most common types of cancer, and it has a poor prognosis. The molecular mechanisms of esophageal cancer progression remain largely unknown. In this study, we aimed to investigate the clinical significance and biological function of tumor necrosis factor receptor-associated factor 6 (TRAF6) in esophageal cancer. Expression of TRAF6 in esophageal cancer was examined, and its correlation with clinicopathological factors and patient prognosis was analyzed. A series of functional and mechanism assays were performed to further investigate the function and underlying mechanisms in esophageal cancer. Expression of TRAF6 was highly elevated in esophageal cancer tissues, and patients with high TRAF6 expression have a significantly shorter survival time than those with low TRAF6 expression. Furthermore, loss-of-function experiments showed that knockdown of TRAF6 significantly reduced the migration and invasion abilities of esophageal cancer cells. Moreover, the pro-oncogenic effects of TRAF6 in esophageal cancer were mediated by the upregulation of AEP and MMP2. Altogether, our data suggest that high expression of TRAF6 is significant for esophageal cancer progression, and TRAF6 indicates poor prognosis in esophageal cancer patients, which might be a novel prognostic biomarker or potential therapeutic target in esophageal cancer.

scholarly journals Regulation of Hippo/YAP signaling and esophageal squamous carcinoma progression by an E3 ubiquitin ligase PARK2

2020 ◽  
Author(s):  
Xiaofeng Zhou ◽  
Yajie Li ◽  
Weilong Wang ◽  
Sujie Wang ◽  
Jinghan Hou ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Ubiquitin Ligase ◽  
Molecular Mechanisms ◽  
Protein Localization ◽  
Clinical Sample ◽  
E3 Ubiquitin Ligase ◽  
Mechanistic Study ◽  
Migration And Invasion ◽  
Hippo Signaling ◽  
Sequencing Analysis

Abstract Background Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies in the world, while the overall five-year survival is less than 20%. Recent genomic sequencing analysis indicated the over-activation of Hippo/YAP signaling might play important roles for the carcinogenic process and progression for ESCC patients. However, little is known about the molecular mechanisms that controls Hippo signaling activity in ESCC. Methods YAP and PARK2 protein level were measured by western blot, while the Hippo classical target genes were measured by real-time PCR. WST1 assay were used to measure cell proliferation, the trans-well and wound healing were used to measure the cell migration and invasion capacity. Protein stability and ubiquitin assay were used to detect the YAP protein ubiquitin and stability. The immuno-precipitation assays were used to detect the protein interactions. Immuno-staining was used to detect the protein localization of YAP and PARK2, while the ubiquitin-based immuno-precipitation assays were used to detect the specific ubiquitination manner of YAP. Results Here, we identify a novel E3 ubiquitin ligase PARK2 as an inhibition factor for Hippo/YAP axis. We find that PARK2 depletion promotes ESCC progression both in vivo and in vitro through Hippo/YAP axis, while PARK2 overexpression suppresses ESCC tumor progression via Hippo signaling. Mechanistic study reveals that PARK2 could interact with YAP in the cytosol and promotes YAP K48-linked ubiquitination at K90 sites, which subsequently promotes YAP protein degradation in ESCC. Clinical sample of ESCC revealed that PARK2 is significantly decreased in ESCC, and relates to good prognosis in ESCC patients. Beside, PARK2 expression negatively correlates with tumor stage and YAP protein expression. Conclusions: Our study identifies an interesting mechanism of Hippo pathway regulation, by which PARK2 modulates ESCC cancer progression, and implies PARK2 could be a novel marker for therapeutics and diagnostics in human ESCC.

scholarly journals LncRNA LINC00342 promotes gastric cancer progression by targeting the miR-545-5p/CNPY2 axis

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Run Liu ◽  
Xianwu Yang
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Growth Factor Signaling ◽  
Ags Cells

Abstract Background This study aimed to explore the role and underlying molecular mechanisms of long non-coding RNA (lncRNA) LINC00342 in gastric cancer (GC). Methods The expression of LINC00342 in GC tissues was evaluated by Quantitative reverse transcription polymerase chain reaction (qRT-PCR). Silencing of LINC00342 was conducted to investigate the effect of LINC00342 in vitro and in vivo. The underlying molecular mechanisms of LINC00342 were determined by dual luciferase reporter assay, Western blotting analysis and rescue experiments. Biological functions of LINC00342 were evaluated by cell counting kit-8 (CCK-8) assay, colony formation assay, wound healing assay and Transwell assays. In addition, a tumor model was used to verify the effect of LINC00342 in tumorigenesis in vivo. Results LINC00342 was significantly upregulated in GC tissues and cell lines. Silencing of LINC00342 efficiently inhibited proliferation, migration and invasion of AGS cells in vitro, and also suppressed the tumorigenesis of GC in vivo. Functional experiments showed that LINC00342 regulated the expression of canopy fibroblast growth factor signaling regulator 2 (CNPY2) by competitively sponging miR-545-5p. Rescue experiments showed that inhibition of miR-545-5p and overexpression of CNPY2 significantly reversed cell phenotypes caused by silencing of LINC00342. Conclusion LINC00342 plays a potential oncogenic role in GC by targeting the miR545-5p/CNPY2 axis, and might act as a novel therapeutic target for GC.

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