Expression analysis and implication of Rab1A in gastrointestinal relevant tumor

Abstract Gastrointestinal cancers have become increasingly prevalent worldwide. Previous studies have reported an oncogenic function of Rab1A in colorectal cancer and hepatocellular carcinomas via the mTOR pathway. However, the exact role of Rab1A in gastrointestinal cancers remains elusive. We detected significantly higher expression of Rab1A in the gastrointestinal tumor tissues compared to that in other cancer types following an in silico analysis of TGCA and GTEX databases. Furthermore, Rab1A was overexpressed in the gastrointestinal tumor tissues compared to the para-tumor tissues. Although Rab1A expression levels were not associated with the tumor-lymph node-metastasis (TNM) stage, Rab1A overexpression in the tumor tissues of a gastric cancer (GC) cohort was strongly correlated with poor prognosis in the patients. In addition, Rab1A knockdown significantly inhibited the in vitro proliferation and migration abilities of GC cells, as well as the growth of GC xenografts in vivo. Furthermore, a positive correlation was observed between Rab1A expression levels and that of different upstream/downstream mTOR targets. Taken together, Rab1A regulates the PI3K-AKT-mTORC1 pathway through the mTORC1 complex consisting of mTORC1, Rheb and Rab1A, and is a promising therapeutic target in GC.

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Positive feedback between lncRNA FLVCR1-AS1 and KLF10 may inhibit pancreatic cancer progression via the PTEN/AKT pathway

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-02097-0 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Jiewei Lin ◽

Shuyu Zhai ◽

Siyi Zou ◽

Zhiwei Xu ◽

Jun Zhang ◽

...

Keyword(s):

Cell Cycle ◽

Pancreatic Cancer ◽

Cell Proliferation ◽

Cancer Progression ◽

Positive Feedback ◽

Molecular Mechanisms ◽

Tumor Tissues ◽

And Migration

Abstract Background FLVCR1-AS1 is a key regulator of cancer progression. However, the biological functions and underlying molecular mechanisms of pancreatic cancer (PC) remain unknown. Methods FLVCR1-AS1 expression levels in 77 PC tissues and matched non-tumor tissues were analyzed by qRT-PCR. Moreover, the role of FLVCR1-AS1 in PC cell proliferation, cell cycle, and migration was verified via functional in vitro and in vivo experiments. Further, the potential competitive endogenous RNA (ceRNA) network between FLVCR1-AS1 and KLF10, as well as FLVCR1-AS1 transcription levels, were investigated. Results FLVCR1-AS1 expression was low in both PC tissues and PC cell lines, and FLVCR1-AS1 downregulation was associated with a worse prognosis in patients with PC. Functional experiments demonstrated that FLVCR1-AS1 overexpression significantly suppressed PC cell proliferation, cell cycle, and migration both in vitro and in vivo. Mechanistic investigations revealed that FLVCR1-AS1 acts as a ceRNA to sequester miR-513c-5p or miR-514b-5p from the sponging KLF10 mRNA, thereby relieving their suppressive effects on KLF10 expression. Additionally, FLVCR1-AS1 was shown to be a direct transcriptional target of KLF10. Conclusions Our research suggests that FLVCR1-AS1 plays a tumor-suppressive role in PC by inhibiting proliferation, cell cycle, and migration through a positive feedback loop with KLF10, thereby providing a novel therapeutic strategy for PC treatment.

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Long non-coding RNA CASC15 promotes HCC progression via modulation of Six1 targeted by miR-2355-5p

10.21203/rs.3.rs-27428/v1 ◽

2020 ◽

Author(s):

Han Hong ◽

Chengjun Sui ◽

Tao Qian ◽

Xiaoyong Xu ◽

Xiang Zhu ◽

...

Keyword(s):

Expression Level ◽

Migration And Invasion ◽

Expression Levels ◽

Invasion And Migration ◽

Downstream Target ◽

Non Coding Rna ◽

And Migration ◽

Hcc Cells

Abstract Background: Long-chain non-coding RNA (LncRNA) plays a key role in the biological processes of tumors. LncRNA CASC15 has been shown to be involved in the development of a variety of tumors. The study aimed to elucidate the mechanism of lncRNA CASC15 in the progression of hepatocellular carcinomas (HCC).Methods: qRT-PCR was used to detect the expression levels of CASC15, miR-2355-5p and Six1 mRNA in HCC tissues and cells. Six1 protein expression levels were detected by Western Blot. CCK-8 experiment, colony formation experiment, Edu staining and Transwell experiment analysis were used to analyze the effects of CASC15, miR-2355-5p and Six1 on cell proliferation, cell invasion and migration. The relationship between CASC15, miR-2355-5p and Six1 was analyzed using bioinformatics analysis and Luciferase.Result: CASC15 was raised in HCC tissues and HCC cells. Down-regulation of CASC15 inhibited the growth, migration, invasion and tumor growth of HCC cells. The expression level of miR-2355-5p was reduced in HCC tissues. In addition, miR-2355-5p inhibitor induced the growth, migration and invasion of HCC cells. MiR-2355-5p was predicted to be a downstream target of CASC15. The expression level of miR-2355-5p was negatively correlated with CASC15 in HCC tumor tissues. Six1 was predicted to be a downstream target of miR-30a-5p. In vitro and in vivo results showed that CASC15/miR-2355-5p can regulate Six1.Conclusion: LncCASC15 regulated the proliferation and invasion of Six1 by binding with miR-2355-5p in HCC, suggesting that CASC15 may be a potential target for HCC.

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The LncRNA CASC11 Promotes Colorectal Cancer Cell Proliferation and Migration by Adsorbing miR-646 and miR-381-3p to Upregulate Their Target RAB11FIP2

Frontiers in Oncology ◽

10.3389/fonc.2021.657650 ◽

2021 ◽

Vol 11 ◽

Author(s):

Wei Zhang ◽

Xiaomin Li ◽

Wenjuan Zhang ◽

Yanxia Lu ◽

Weihao Lin ◽

...

Keyword(s):

Colorectal Cancer ◽

Target Genes ◽

Suppressive Effect ◽

Luciferase Reporter ◽

Expression Levels ◽

Non Coding Rna ◽

Potential Biomarker ◽

And Migration

BackgroundWe previously reported that the long non-coding RNA (lncRNA) CASC11 promotes colorectal cancer (CRC) progression as an oncogene by binding to HNRNPK. However, it remains unknown whether CASC11 can act as a competitive endogenous RNA (ceRNA) in CRC. In this study, we focused on the role of CASC11 as a ceRNA in CRC by regulating miR-646 and miR-381-3p targeting of RAB11FIP2.MethodsWe identified the target microRNAs (miRNAs) of CASC11 and the target genes of miR-646 and miR-381-3p using bioinformatic methods. A dual-luciferase reporter assay was performed to validate the target relationship. Quantitative real-time PCR (qRT-PCR), western blotting (WB), and immunohistochemistry (IHC) were used to measure the RNA and protein expression levels. Rescue experiments in vitro and in vivo were performed to investigate the influence of the CASC11/miR-646 and miR-381-3p/RAB11FIP2 axis on CRC progression.ResultsWe found that CASC11 binds to miR-646 and miR-381-3p in the cytoplasm of CRC cells. Moreover, miR-646 and miR-381-3p inhibitors reversed the suppressive effect of CASC11 silencing on CRC growth and metastasis in vitro and in vivo. We further confirmed that RAB11FIP2 is a mutual target of miR-646 and miR-381-3p. The expression levels of CASC11 and RAB11FIP2 in CRC were positively correlated and reciprocally regulated. Further study showed that CASC11 played an important role in regulating PI3K/AKT pathway by miR-646 and miR-381-3p/RAB11FIP2 axis.ConclusionOur study showed that CASC11 promotes the progression of CRC as a ceRNA by sponging miR-646 and miR-381-3p. Thus, CASC11 is a potential biomarker and a therapeutic target of CRC.

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Transferrin-Conjugated Erianin-Loaded Liposomes Suppress the Growth of Liver Cancer by Modulating Oxidative Stress

Frontiers in Oncology ◽

10.3389/fonc.2021.727605 ◽

2021 ◽

Vol 11 ◽

Author(s):

Anhui Yang ◽

Zhen Sun ◽

Rui Liu ◽

Xin Liu ◽

Yue Zhang ◽

...

Keyword(s):

Liver Cancer ◽

Tumor Targeting ◽

Tumor Model ◽

Aqueous Solubility ◽

Ethanol Injection ◽

Expression Levels ◽

Tumor Tissues ◽

Induced Apoptosis

BackgroundLiver cancer is one of the most malignant human cancers, with few treatments and a poor prognosis. Erianin (ERN) is a natural compound with multiple pharmacological activities that has been reported to have numerous excellent effects against liver cancer in experimental systems. However, its application in vivo has been limited due to its poor aqueous solubility and numerous off-target effects. This study aimed to improve the therapeutic efficacy of ERN by developing novel ERN-loaded tumor-targeting nanoparticles.ResultsIn this study, ERN was loaded into liposomes by ethanol injection (LP-ERN), and the resulting LP-ERN nanoparticles were treated with transferrin to form Tf-LP-ERN to improve the solubility and enhance the tumor-targeting of ERN. LP-ERN and Tf-LP-ERN nanoparticles had smooth surfaces and a uniform particle size, with particle diameters of 62.60 nm and 88.63 nm, respectively. In HepG2 and SMMC-7721 cells, Tf-LP-ERN induced apoptosis, decreased mitochondrial membrane potentials and increased ERN uptake more effectively than free ERN and LP-ERN. In xenotransplanted mice, Tf-LP-ERN inhibited tumor growth, but had a minimal effect on body weight and organ morphology. In addition, Tf-LP-ERN nanoparticles targeted tumors more effectively than free ERN and LP-ERN nanoparticles, and in tumor tissues Tf-LP-ERN nanoparticles promoted the cleavage PARP-1, caspase-3 and caspase-9, increased the expression levels of Bax, Bad, PUMA, and reduced the expression level of Bcl-2. Moreover, in the spleen of heterotopic tumor model BALB/c mice, ERN, LP-ERN and Tf-LP-ERN nanoparticles increased the expression levels of Nrf2, HO-1, SOD-1 and SOD-2, but reduced the expression levels of P-IKKα+β and P-NF-κB, with Tf-LP-ERN nanoparticles being most effective in this regard. Tf-LP-ERN nanoparticles also regulated the expression levels of TNF-α, IL-10 and CCL11 in serum.ConclusionTf-LP-ERN nanoparticles exhibited excellent anti-liver cancer activity in vivo and in vitro by inducing cellular apoptosis, exhibiting immunoregulatory actions, and targeting tumor tissues, and did so more effectively than free ERN and LP-ERN nanoparticles. These results suggest that the clinical utility of a Tf-conjugated LP ERN-delivery system for the treatment of liver cancer warrants exploration.

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Eupatilin Inhibits Renal Cancer Growth by Downregulating MicroRNA-21 through the Activation of YAP1

BioMed Research International ◽

10.1155/2019/5016483 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Weifeng Zhong ◽

Zhiming Wu ◽

Nanhui Chen ◽

Kaihua Zhong ◽

Yifeng Lin ◽

...

Keyword(s):

Renal Cancer ◽

Nude Mice ◽

Underlying Mechanism ◽

Renal Tumors ◽

Anticancer Effects ◽

Tumor Tissues ◽

And Migration ◽

Lower Expression

Renal cell carcinoma (RCC) is the second most common human urinary tumor. Eupatilin is the main active ingredient of the traditional Chinese medicineArtemisia asiatica. The effect of Eupatilin on RCC and the underlying mechanism remain unknown. Here, we investigated the anticancer effects and mechanisms of Eupatilin in RCCin vivoandin vitro, laying an experimental foundation for the clinical application of Eupatilin in the treatment of RCC. The results showed that Eupatilin significantly inhibited 786-O cell viability and migration and promoted apoptosis. Eupatilin inhibited the expression of miR-21 in 786-O cells, and overexpression of miR-21 suppressed the effect of Eupatilin on viability, apoptosis, and migration in 786-O cells. Eupatilin inhibited the growth of renal tumors in nude mice by downregulating miR-21. YAP1, which was identified as a target of miR-21, showed significantly lower expression in RCC tissues than in healthy tissues. miR-21 significantly inhibited YAP1 protein expression in 786-O cells and tumor tissues isolated from nude mice, and YAP1 attenuated the effect of miR-21 on the viability, apoptosis, and migration of 786-O cells. In conclusion, Eupatilin inhibited the expression of miR-21, which mediated the proapoptotic and antimigratory effects of Eupatilin by suppressing YAP1 in renal cancer cells. These results suggested that Eupatilin could be a potent agent for the treatment of RCC.

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MicroRNA-29a Promotes Pancreatic Cancer Growth by Inhibiting Tristetraprolin

Cellular Physiology and Biochemistry ◽

10.1159/000430389 ◽

2015 ◽

Vol 37 (2) ◽

pp. 707-718 ◽

Cited By ~ 19

Author(s):

Xian-Jun Sun ◽

Bing-Yan Liu ◽

Shuo Yan ◽

Ting-Hui Jiang ◽

Hui-Qin Cheng ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Progression ◽

Ectopic Expression ◽

Inflammatory Factors ◽

Aberrant Expression ◽

Mesenchymal Transition ◽

Tumor Tissues ◽

And Migration

Background/Aims: The microRNA (miR) 29 family has been studied extensively for its involvement in several diseases, and aberrant expression of its members is associated with tumorigenesis and cancer progression. Here, we examined the role of miR-29a in pancreatic cancer and the involvement of tristetraprolin (TTP). Methods: We monitored miR-29a and TTP expression in pancreatic cancer by qRT-PCR and western blotting. The effect of miR-29a on pancreatic cancer was determined through MTT assay and migration assay. The results were validated in the tumorigenesis model. Results: We found that miR-29a was up regulated in pancreatic tumor tissues and cell lines and positively correlated with metastasis. Ectopic expression of miR-29a increased the expression of pro-inflammatory factors and epithelial-mesenchymal transition (EMT) markers, through down regulating TTP. TTP was down regulated in tumor tissues, and its ectopic expression decreased cell viability and migration in vitro, inhibited tumor growth and the EMT phenotype in vivo, and reversed the effect of miR-29a on tumor cell proliferation and invasion in vitro and in vivo. Conclusion: Our results suggest that miR-29a acts as an oncogene by down regulating TTP and provide the basis for further studies exploring the potential of miR-29a and TTP as biomarkers and targets for the treatment of pancreatic cancer.

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Lnc-RNA CASC15 promotes HCC progression via modulation of Six1 targeted by miR-2355-5p

10.21203/rs.3.rs-27428/v2 ◽

2020 ◽

Author(s):

Han Hong ◽

Chengjun Sui ◽

Tao Qian ◽

Xiaoyong Xu ◽

Xiang Zhu ◽

...

Keyword(s):

Expression Level ◽

Migration And Invasion ◽

Expression Levels ◽

Invasion And Migration ◽

Downstream Target ◽

Non Coding Rna ◽

And Migration ◽

Hcc Cells

Abstract Background: Long-chain non-coding RNA (LncRNA) plays a key role in the biological processes of tumors. LncRNA CASC15 has been shown to be involved in the development of a variety of tumors. The study aimed to elucidate the mechanism of lncRNA CASC15 in the progression of hepatocellular carcinomas (HCC). Methods: qRT-PCR was used to detect the expression levels of CASC15, miR-2355-5p and Six1 mRNA in HCC tissues and cells. Six1 protein expression levels were detected by Western Blot. CCK-8 experiment, colony formation experiment, Edu staining and Transwell experiment analysis were used to analyze the effects of CASC15, miR-2355-5p and Six1 on cell proliferation, cell invasion and migration. The relationship between CASC15, miR-2355-5p and Six1 was analyzed using bioinformatics analysis and Luciferase. Result: CASC15 was raised in HCC tissues and HCC cells. Down-regulation of CASC15 inhibited the growth, migration, invasion and tumor growth of HCC cells. The expression level of miR-2355-5p was reduced in HCC tissues. In addition, miR-2355-5p inhibitor induced the growth, migration and invasion of HCC cells. MiR-2355-5p was predicted to be a downstream target of CASC15. The expression level of miR-2355-5p was negatively correlated with CASC15 in HCC tumor tissues. Six1 was predicted to be a downstream target of miR-30a-5p. In vitro and in vivo results showed that CASC15/miR-2355-5p can regulate Six1.Conclusion: LncCASC15 regulated the proliferation and invasion of Six1 by binding with miR-2355-5p in HCC, suggesting that CASC15 may be a potential target for HCC.

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Knockdown of RhoC Inhibits Oral Squamous Cell Carcinoma Cell Invasion and Metastasis via Regulation of HMGA2

Journal of Oncology ◽

10.1155/2021/6644077 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Feng Gao ◽

Panpan Yin ◽

Yanlin Wu ◽

Jinlin Wen ◽

Ying Su ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Growth ◽

Invasion And Metastasis ◽

Invasion And Migration ◽

Node Metastasis ◽

Tumor Tissues ◽

And Migration ◽

Rhoc Expression

Ras homolog family member C (RhoC) is an important component of intracellular signal transduction and its overexpression has been reported to be involved in regulating tumor proliferation, invasion, and metastasis in various malignant tumors. However, its role and underlying mechanism in oral squamous cell carcinoma (OSCC) still remain obscure. In our study, RhoC expression, its relation with clinical stages, and survival rate in OSCC were analyzed using datasets from The Cancer Genome Atlas (TCGA). Next, a RhoC knockdown cell model was established in vitro, and the effects of RhoC knockdown in OSCC cells were detected by the MTT assay, colony formation assay, transwell invasion assay, scratch assay, and F-actin phalloidin staining. An in vivo tongue-xenografted nude mouse model was established to measure the effects of knockdown of RhoC on tumor cell growth and lymph node metastasis. A mechanism study was conducted by real-time PCR and immunocytochemistry. The results of TCGA analysis showed that RhoC was overexpressed in OSCC tumor tissues. In vitro assays indicated that knockdown of RhoC did not have much effect on OSCC cell growth but significantly suppressed cell colony formation, invasion, and migration abilities, and F-actin polymerization was also reduced. The tongue-xenografted in vivo model demonstrated that knockdown of RhoC suppressed OSCC cell growth and inhibited metastasis to the superficial cervical lymph nodes. Further mechanism studies showed that knockdown of RhoC downregulated HMGA2 expression, and HMGA2 expression was highly correlated with RhoC expression in OSCC tumor tissues via the analysis of TCGA datasets. Overall, our study showed that knockdown of RhoC inhibited OSCC cells invasion and migration in vitro and OSCC cell growth and lymph node metastasis in vivo. Moreover, the potential mechanisms involved in these activities may be related to the regulation of HMGA2 expression. The RhoC gene could serve as a promising therapeutic target for OSCCs in the future.

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Long Non-coding RNA FIRRE Acts as a miR-520a-3p Sponge to Promote Gallbladder Cancer Progression via Mediating YOD1 Expression

Frontiers in Genetics ◽

10.3389/fgene.2021.674653 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shuqing Wang ◽

Yang Wang ◽

Shouhua Wang ◽

Huanjun Tong ◽

Zhaohui Tang ◽

...

Keyword(s):

Gallbladder Cancer ◽

Cancer Progression ◽

Clinical Stage ◽

Luciferase Reporter ◽

Tumor Tissues ◽

Rna Immunoprecipitation ◽

Reporter Assays ◽

And Migration

ObjectivesThe role of lncRNAs in gallbladder cancer (GBC) remains poorly understood. In this study, we explored the function of functional intergenic repeating RNA element (FIRRE) in GBC.Materials and MethodsWhole transcriptome resequencing was performed in three pairs of GBC tissues and adjacent non-tumor tissues. lncRNA FIRRE expression was verified by real-time PCR. The function of FIRRE in GBC was evaluated by experiments in vitro and in vivo. The mechanism of FIRRE was investigated via fluorescent in situ hybridization, RNA pull-down, dual luciferase reporter assays, and RNA immunoprecipitation.ResultsFIRRE level was dramatically increased in GBC tissues compared to that in the adjacent non-tumor tissues. High expression of FIRRE was closely related to clinical stage and poor prognosis in GBC patients. Moreover, FIRRE remarkably enhanced proliferation and migration, and inhibited apoptosis of GBC cells. Mechanistically, FIRRE modulated YOD1 expression by sponging miR-520a-3p, thus contributing to the development of GBC.ConclusionOur data revealed that FIRRE might act as a novel mediator in GBC progression by sponging miR-520a-3p and regulating YOD1. FIRRE might be regarded as a potential diagnostic marker or target for GBC treatment.

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SNHG1 promotes MPP+-induced cytotoxicity by regulating PTEN/AKT/mTOR signaling pathway in SH-SY5Y cells via sponging miR-153-3p

Biological Research ◽

10.1186/s40659-019-0267-y ◽

2020 ◽

Vol 53 (1) ◽

Cited By ~ 7

Author(s):

Jun Zhao ◽

Lijiao Geng ◽

Yong Chen ◽

Chunfang Wu

Keyword(s):

Signaling Pathway ◽

Regulatory Networks ◽

Mtor Signaling ◽

Luciferase Reporter ◽

Mtor Signaling Pathway ◽

Expression Levels ◽

Promising Therapeutic Target ◽

Rna Immunoprecipitation

Abstract Background Long non-coding RNA small molecule RNA host gene 1 (SNHG1) was previously identified to be relevant with Parkinson’s disease (PD) pathogenesis. This work aims to further elucidate the regulatory networks of SNHG1 involved in PD. Methods 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-hydrochloride (MPTP)-induced mice and 1-methyl-4-phenylpyridinium (MPP+)-treated SH-SY5Y cells were respectively constructed as the in vivo and in vitro PD models. Expression levels of SNHG1 and miR-153-3p were detected by qRT-PCR. Protein expression levels of phosphate and tension homology deleted on chromosome ten (PTEN) were measured by western blotting assay. Cell viability and apoptosis were determined by MTT and flow cytometry assays. The interactions among SNHG1, miR-153-3p and PTEN were identified by luciferase reporter assay, RNA immunoprecipitation, and/or RNA pull-down analysis. Results Increased SNHG1 expression was found in midbrain of MPTP-induced PD mice and MPP+-treated SH-SY5Y cells. Overexpression of SNHG1 lowered viability and enhanced apoptosis in MPP+-treated SH-SY5Y cells. Moreover, SNHG1 acted as a molecular sponge to inhibit the expression of miR-153-3p. Furthermore, miR-153-3p-mediated suppression of MPP+-induced cytotoxicity was abated following SNHG1 up-regulation. Additionally, PTEN was identified as a direct target of miR-153-3p, and SNHG1 could serve as a competing endogenous RNA (ceRNA) of miR-153-3p to improve the expression of PTEN. Besides, enforced expression of PTEN displayed the similar functions as SNHG1 overexpression in regulating the viability and apoptosis of MPP+-treated SH-SY5Y cells. Finally, SNHG1 was found to activate PTEN/AKT/mTOR signaling pathway in SH-SY5Y cells by targeting miR-153-3p. Conclusion SNHG1 aggravates MPP+-induced cellular toxicity in SH-SY5Y cells by regulating PTEN/AKT/mTOR signaling via sponging miR-153-3p, indicating the potential of SNHG1 as a promising therapeutic target for PD.

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