scholarly journals Pyrroline-5-Carboxylate Reductase-2 Promotes Colorectal Cancer Progression via Activating PI3K/AKT/mTOR Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Feng Yin ◽  
Xiaoxia Huang ◽  
Yi Xuan
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Caspase 3 ◽  
Clinical Information ◽  
Nodal Metastasis ◽  
Mtor Pathway ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Information Cell ◽  
Carboxylate Reductase

Aim. The aim of this study was to investigate the effect and underlying pathway of pyrroline-5-carboxylate reductase-2 (PYCR2) on colorectal cancer (CRC). Methods. The Cancer Genome Atlas (TCGA) database was used to analyze PYCR2 expression levels and clinical information. Cell proliferation was evaluated using colony forming and EdU assay. Cell apoptosis rate was determined using flow cytometry. Cell migration and invasion were measured by performing a Transwell assay, and PYCR2, MMP-2, MMP-9, Bax, cleaved caspase-3, Bcl-2, cleaved PARP, p-PI3K, PI3K, p-AKT, AKT, p-mTOR, and mTOR protein levels were detected by Western blot. Results. A review of the TCGA database revealed that PYCR2 was highly expressed in CRC patients and that high PYCR2 expression was associated with advanced stage, adenocarcinoma, nodal metastasis, and poor survival rate. Moreover, PYCR2 knockdown reduced cell viability, proliferation, migration, and invasion and increased apoptosis. Additionally, PYCR2 knockdown increased Bax, cleaved caspase-3, and cleaved PARP levels and decreased Bcl-2, MMP-2, MMP-9, p-PI3K, p-AKT, and p-mTOR levels in CRC cells. Effects of silencing PYCR2 on proliferation, migration, invasion, apoptosis, and the PI3K/AKT/mTOR pathway in CRC cells were all reversed using a PI3K activator (740Y-P). Conclusion. PYCR2 was highly expressed in CRC, and its knockdown suppressed CRC tumorigenesis via inhibiting the activation of PI3K/AKT/mTOR pathway. This finding provides a new theoretical foundation for the treatment of CRC.

scholarly journals Apoptotic Effects of Xanthium strumarium via PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Juyoung Kim ◽  
Kyung Hee Jung ◽  
Hyung Won Ryu ◽  
Doo-Young Kim ◽  
Sei-Ryang Oh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Caspase 3 ◽  
Mtor Pathway ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Mechanistic Study ◽  
Migration And Invasion ◽  
Xanthium Strumarium ◽  
Apoptotic Effects ◽  
Hcc Cells

Xanthium strumarium (XS) has been traditionally used as a medicinal herb for treating inflammatory diseases, such as appendicitis, chronic bronchitis, rheumatism, and rhinitis. In this study, we yielded ethanol extracts from XS and investigated whether they could inhibit the progression of hepatocellular carcinoma (HCC) and its underlying mechanism. The XS-5 and XS-6 extracts dose-dependently inhibited the growth and proliferation in HCC cell lines. The apoptotic effects of them were observed via increased levels of cleaved caspase-3 and cleaved PARP, as well as elevated numbers of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling- (TUNEL-) positive apoptotic cells. They also decreased XIAP and Mcl-1 expression via loss of mitochondrial membrane potential. Additionally, they inhibited the invasion and migration of HCC cells. In an ex vivo model, the extracts significantly inhibited tumor cell growth and induced apoptosis by increasing the expression of the cleaved caspase-3. A mechanistic study revealed that they effectively suppressed PI3K/AKT/mTOR signaling pathways in HCC cells. Taken together, our findings demonstrate that they could efficiently not only induce apoptosis but also inhibit cell growth, migration, and invasion of human HCC cells by blocking the PI3K/AKT/mTOR pathway. We suggest XS-5 and XS-6 as novel natural anti-HCC agents.

scholarly journals Decreased level of miR-1301 promotes colorectal cancer progression via activation of STAT3 pathway

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Fangfang Yang ◽  
Hua Wang ◽  
Bianbian Yan ◽  
Tong Li ◽  
Lulu Min ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Progression ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Aberrant Expression ◽  
Cell Migration And Invasion ◽  
Lovo Cells ◽  
Colorectal Cancer Progression

Abstract The molecular pathogenesis of colorectal cancer (CRC) has been widely investigated in recent years. Accumulating evidence has indicated that microRNA (miRNA) dysregulation participates in the processes of driving CRC initiation and progression. Aberrant expression of miR-1301 has been found in various tumor types. However, its role in CRC remains to be elucidated. In the present study, we identified miR-1301 was enriched in normal colorectal tissues and significantly down-regulated in CRC. Decreased level of miR-1301 strongly correlated with aggressive pathological characteristics, including advanced stage and metastasis. Bioinformatics and dual luciferase assay demonstrated that STAT3 is a direct target of miR-1301. Gain and loss-of-function assays showed that miR-1301 had no effect on cell proliferation. Overexpression of miR-1301 suppressed cell migration and invasion capacity of pSTA3-positive LoVo cells, but not pSTAT3-negative SW480 cells, while inhibition of miR-1301 consistently promoted cell migration and invasion in both cell lines. Additionally, miR-1301 inhibition restored the suppressed migration and invasion of STAT3- knockdown LoVo cells. MiR-1301 functioned as a tumor suppressor to modulate the IL6/STAT3 signaling pathway. In summary, this study highlights the significant role of miR- 1301/STAT3 axis in CRC metastasis.

scholarly journals Circ_0003266 sponges miR-503-5p to suppress colorectal cancer progression via regulating PDCD4 expression

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Caihong Wen ◽  
Xiaoqing Feng ◽  
Honggang Yuan ◽  
Yong Gong ◽  
Guangsheng Wang
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Progression ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Pdcd4 Expression ◽  
Novel Target

Abstract Background Circular RNAs (circRNAs) feature prominently in tumor progression. However, the biological function and molecular mechanism of circ_0003266 in colorectal cancer (CRC) require further investigation. Methods Circ_0003266 expression in 46 pairs CRC tissues / adjacent tissues, and CRC cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR); after circ_0003266 was overexpressed or knocked down in CRC cells, cell proliferation, apoptosis, migration, and invasion were evaluated by the cell counting kit-8 (CCK-8), flow cytometry, and Transwell assays, respectively; the interaction among circ_0003266, miR-503-5p, and programmed cell death 4 (PDCD4) was confirmed using bioinformatics analysis and dual-luciferase reporter assay; PDCD4 protein expression in CRC cells was quantified using Western blot. Results Circ_0003266 was significantly lowly expressed in CRC tissues and cell lines. Circ_0003266 overexpression markedly repressed CRC cell proliferation, migration, and invasion, and accelerated the cell apoptosis, but its overexpression promoted the malignant phenotypes of CRC cells. PDCD4 was a direct target of miR-503-5p and circ_0003266 promoted PDCD4 expression by competitively sponging miR-503-5p. Conclusion Circ_0003266 suppresses the CRC progression via sponging miR-503-5p and regulating PDCD4 expressions, which suggests that circ_0003266 may serve as a novel target for the treatment of CRC.

scholarly journals PRKAR1B-AS2 Long Noncoding RNA Promotes Tumorigenesis, Survival, and Chemoresistance via the PI3K/AKT/mTOR Pathway

2021 ◽  
Vol 22 (4) ◽  
pp. 1882
Author(s):  
Abdelrahman M. Elsayed ◽  
Emine Bayraktar ◽  
Paola Amero ◽  
Salama A. Salama ◽  
Abdelaziz H. Abdelaziz ◽  
...  
Keyword(s):  
Mouse Model ◽  
Long Noncoding Rna ◽  
Proteomic Analysis ◽  
Noncoding Rna ◽  
Mtor Pathway ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Physical Interaction ◽  
Cisplatin Sensitivity

Many long noncoding RNAs have been implicated in tumorigenesis and chemoresistance; however, the underlying mechanisms are not well understood. We investigated the role of PRKAR1B-AS2 long noncoding RNA in ovarian cancer (OC) and chemoresistance and identified potential downstream molecular circuitry underlying its action. Analysis of The Cancer Genome Atlas OC dataset, in vitro experiments, proteomic analysis, and a xenograft OC mouse model were implemented. Our findings indicated that overexpression of PRKAR1B-AS2 is negatively correlated with overall survival in OC patients. Furthermore, PRKAR1B-AS2 knockdown-attenuated proliferation, migration, and invasion of OC cells and ameliorated cisplatin and alpelisib resistance in vitro. In proteomic analysis, silencing PRKAR1B-AS2 markedly inhibited protein expression of PI3K-110α and abrogated the phosphorylation of PDK1, AKT, and mTOR, with no significant effect on PTEN. The RNA immunoprecipitation detected a physical interaction between PRKAR1B-AS2 and PI3K-110α. Moreover, PRKAR1B-AS2 knockdown by systemic administration of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine nanoparticles loaded with PRKAR1B-AS2–specific small interfering RNA enhanced cisplatin sensitivity in a xenograft OC mouse model. In conclusion, PRKAR1B-AS2 promotes tumor growth and confers chemoresistance by modulating the PI3K/AKT/mTOR pathway. Thus, targeting PRKAR1B-AS2 may represent a novel therapeutic approach for the treatment of OC patients.

scholarly journals lncRNA NORAD Contributes to Colorectal Cancer Progression by Inhibition of miR-202-5p

2018 ◽  
Vol 26 (9) ◽  
pp. 1411-1418 ◽  
Author(s):  
Jie Zhang ◽  
Xiao-Yan Li ◽  
Ping Hu ◽  
Yuan-Sheng Ding
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Cancer Metastasis ◽  
Cellular Proliferation ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Competing Endogenous Rna

Previous study indicates that long noncoding RNA NORAD could serve as a competing endogenous RNA to pancreatic cancer metastasis. However, its role in colorectal cancer (CRC) needs to be investigated. In the present study, we found that the expression of NORAD was significantly upregulated in CRC tissues. Furthermore, the expression of NORAD was positively related with CRC metastasis and patients’ poor prognosis. Knockdown of NORAD markedly inhibited CRC cell proliferation, migration, and invasion but induced cell apoptosis in vitro. In vivo experiments also indicated an inhibitory effect of NORAD on tumor growth. Mechanistically, we found that NORAD served as a competing endogenous RNA for miR-202-5p. We found that there was an inverse relationship between the expression of NORAD and miR-202-5p in CRC tissues. Moreover, overexpression of miR-202-5p in SW480 and HCT116 cells significantly inhibited cellular proliferation, migration, and invasion. Taken together, our study demonstrated that the NORAD/miR-202-5p axis plays a pivotal function on CRC progression.

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.

Claudin14 promotes colorectal cancer progression via the PI3K/AKT/mTOR pathway

Neoplasma ◽  
2021 ◽  
Author(s):  
Tian-Yu Qiao ◽  
Zi-Ming Yuan ◽  
Tian-Yi Ma ◽  
Han-Qing Hu ◽  
Yi-Hao Zhu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Mtor Pathway ◽  
Colorectal Cancer Progression

scholarly journals MicroRNA-18a promotes cancer progression through SMG1 suppression and mTOR pathway activation in nasopharyngeal carcinoma

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
ShiJuan Mai ◽  
RuoWen Xiao ◽  
Lu Shi ◽  
XiaoMin Zhou ◽  
Te Yang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cancer Progression ◽  
Ectopic Expression ◽  
Mtor Pathway ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Antitumor Effects ◽  
Barr Virus ◽  
Epstein Barr

Abstract miR-18a has been reported to be upregulated in nasopharyngeal carcinoma (NPC) tissues by microarray assays. However, the roles and the underlying mechanisms of miR-18a in NPC remain poorly understood. Here we demonstrated by real-time RT-PCR that miR-18a expression is upregulated in NPC tissues, and positively correlated with tumor size and TNM stage. Moreover, miR-18a expression could be upregulated by NF-κB activation or Epstein-Barr virus encoded latent membrane protein 1 expression. The ectopic expression of miR-18a promoted NPC cell proliferation, migration and invasion, while the repression of miR-18a had opposite effects. Candidate genes under regulation by miR-18a were screened out through a whole-genome microarray assay, further identified by a reporter assay and verified in clinical samples. SMG1, a member of the phosphoinositide 3-kinase-related kinases family and an mTOR antagonist, was identified as functional target of miR-18a. Our results confirmed that miR-18a exerts its oncogenic role through suppression of SMG1 and activation of mTOR pathway in NPC cells. Importantly, in vivo xenograft tumor growth in nude mice was effectively inhibited by intratumor injection of miR-18a antagomir. Our data support an oncogenic role of miR-18a through a novel miR-18a/SMG1/mTOR axis and suggest that the antitumor effects of antagomir-18a may make it suitable for NPC therapy.

scholarly journals SNORA71A Promotes Colorectal Cancer Cell Proliferation, Migration, and Invasion

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Zhengxiang Zhang ◽  
Yunxiang Tao ◽  
Qingling Hua ◽  
Juan Cai ◽  
Xiaobing Ye ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Sensory Perception ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Integrated Analysis ◽  
Small Rna Sequencing ◽  
Chemical Stimulus ◽  
Normal Tissues

Small nucleolar RNAs (snoRNAs) play a crucial role during colorectal cancer (CRC) development. The study of SNORA71A is few, and its role in CRC is unknown. This study focused on screening abnormal snoRNAs in CRC and exploring the role of key snoRNA in CRC. The expression pattern of snoRNAs in 3 CRC and 3 normal colon tissues was detected via small RNA sequencing. The six candidate snoRNAs were identified by quantitative PCR (qPCR). Subsequently, the expression level of SNORA71A was further verified through the Cancer Genome Atlas (TCGA) data analysis and qPCR. The CCK8 and transwell assays were used to detect the functional role of SNORA71A in CRC cells. The integrated analysis of snoRNA expression profile indicated that a total 107 snoRNAs were significantly differentially expressed (DE) in CRC tissues compared with normal tissues, including 45 upregulated and 62 downregulated snoRNAs. Bioinformatics analysis revealed that the DE snoRNAs were mainly implicated in “detection of chemical stimulus involved in sensory perception of smell” and “sensory perception of smell” in the biological process. The DE snoRNAs were preferentially enriched in “olfactory transduction” and “glycosphingolipid biosynthesis-ganglio series pathway.” The expression of SNORA71A was upregulated in CRC tissues and cells. SNORA71A expression showed statistically significant correlations with TNM stage ( P = 0.0196 ) and lymph node metastasis ( P = 0.0189 ) and can serve as biomarkers for CRC. Importantly, SNORA71A significantly facilitated the CRC cell proliferation, migration, and invasion. Our findings indicate that SNORA71A screened by sequencing acted as an oncogene and promoted proliferation, migration, and invasion ability of CRC cells.

Sign in / Sign up

Export Citation Format

Share Document