The Cultivation in vitro of Tumor Tissues and Normal Tissues of Picea glauca1

Abstract Context.—RAAG12 is a primate-restricted N-linked carbohydrate antigen present on multiple membrane-associated proteins. RAAG12 is recognized by the RAV12 monoclonal antibody. RAV12 binds to RAAG12-expressing gastrointestinal adenocarcinomas, modifies growth factor-mediated signaling, induces oncotic cell death in vitro, and has antitumor activity toward gastrointestinal tumor xenografts. Objective.—To determine the expression pattern of RAAG12 in normal and tumor tissue to identify indications for clinical study and potential safety issues. Design.—Immunohistochemistry of 36 normal human tissues and a broad range of tumor tissues to profile RAAG12 expression. Results.—More than 90% of colon, gastric, and pancreatic adenocarcinomas expressed RAAG12, and expression was uniform in most samples. Expression of RAAG12 at lower frequency and/or uniformity was observed in other cancers, including esophageal, ovarian, liver, breast, and prostate carcinomas and adenocarcinomas. Similar RAAG12 expression was observed between primary and metastatic colon adenocarcinomas. No staining was seen on cardiovascular, endocrine, neuromuscular, hematopoietic, or nervous system tissue from non–tumor-bearing individuals. RAAG12 was expressed on mucosal and glandular/ductal epithelium. The gastrointestinal tract mucosa and pancreatic/biliary ducts displayed the most uniform reactivity. RAAG12 exhibited differential subcellular localization in these normal, compared with tumor, tissues. Normal polarized epithelia primarily displayed apical membrane and cytoplasmic staining, whereas tumors exhibited whole membrane staining that increased with decreasing differentiation. Conclusions.—High expression of RAAG12 on tumors of gastrointestinal origin suggests these cancers are appropriate targets for RAV12 therapy. Differential subcellular location of RAAG12 on normal epithelia may limit accessibility of RAV12 to the subset of normal tissues that exhibit antigen expression.

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Targeting UCP2 Suppresses the FAK Signaling and Progression of Human Head and Neck Cancer Cells

Clinical Oncology and Research ◽

10.31487/j.cor.2020.04.09 ◽

2020 ◽

pp. 1-8

Author(s):

Yunfeng Zhao ◽

Cherie Ann Nathan ◽

Chunjing Zhang ◽

Hongyan Du ◽

Manikandan Panchatcharam ◽

...

Keyword(s):

Head And Neck ◽

Cancer Cells ◽

Cancer Progression ◽

Uncoupling Protein ◽

Human Head ◽

Atp Production ◽

Normal Tissues ◽

Tumor Tissues ◽

Lactate Formation

Background: New adjuvant therapies for human head and neck (H&N) cancer to improve the quality of life of the patients are in great demand. Our early studies have demonstrated that uncoupling protein 2 (UCP2) is upregulated in the tumor tissues of H&N cancer compared to the adjacent normal tissues; however, the role of UCP2 in H&N cancer has not been studied. Objective: In this manuscript, we aim to examine whether UCP2 contributes to H&N cancer progression in vitro. Methods: We generated UCP2 stable knockdown H&N cancer cells and detected the effects of UCP2 inhibition on cell proliferation, migration, invasion, 3D spheroid formation, and the sensitivity to a chemodrug treatment. Results: Knockdown of UCP2 suppressed the progression of H&N cancer in vitro, which might be mediated via the following mechanism: 1) increased the G1 phase whereas decreased the S phase of the cell cycle, which could be mediated by suppression of the G1/S regulators including CDK4/6 and cyclin D1. 2) Decreased mitochondrial oxygen consumption, ATP production, and lactate formation, which is consistent with the downregulation of c-Myc. 3) FAK may serve as the upstream signaling molecule, and its action was mediated by Akt and ERK. Conclusions: Our studies first demonstrate that targeting UCP2 may suppress H&N cancer progression in vitro.

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LncRNA DUXAP8 promotes the progression of laryngeal cancer through targeting miR-384/ POU2F1 axis

10.21203/rs.3.rs-132474/v1 ◽

2020 ◽

Author(s):

Zhanfeng Yan ◽

Xiaohui Wen ◽

Jinsheng Dai ◽

Jinfeng Liu ◽

Pengpeng Hao ◽

...

Keyword(s):

Cell Proliferation ◽

Laryngeal Cancer ◽

Tumor Model ◽

Inhibitory Effect ◽

Luciferase Reporter ◽

Normal Tissues ◽

Tumor Tissues ◽

High Level

Abstract Background Laryngeal cancer is the highest incidence of head and neck cancers in the world. Increasing evidences have demonstrated that long non-coding RNAs (lncRNAs) play crucial roles in the progression of laryngeal cancer. Despite of the essential role of lncRNA DUXAP8 in many human cancers, its function and specific mechanisms in laryngeal cancer are poorly understood. Methods Differentially expression analysis of lncRNAs in GSE59652 dataset was performed by using limma package of R language. The expression of DUXAP8, miR-384 and candidate mRNAs was evaluated by qRT-PCR. Luciferase reporter assay and RIP assay were performed to determine the direct correlation between DUXAP8, miR-384 and POU2F1. Cell proliferation of laryngeal cancer cell lines TU212 and TU177 cells was evaluated by using CCK-8 assay, colony formation assay and EdU staining assay. Xenograft tumor model in vivo and rescue experiments were performed to explore the function and mechanisms of DUXAP8 in laryngeal cancer. Results The expression of DUXAP8 in tumor tissues was higher than that in adjacent normal tissues. High level of DUXAP8 was closely correlated to the worse prognosis of laryngeal cancer patients. Knockdown of DUXAP8 inhibited the proliferation of TU212 and TU177 cells in vitro, as well as tumor growth in vivo. Furthermore, overexpression of POU2F1 significantly attenuated the inhibitory effect of sh-DUXAP8 on cell proliferation of TU212 and TU177 cells. In addition, sh-DUXAP8 significantly decreased the expression of DUXAP8 and POU2F1, while increased miR-384 expression in tumor tissues compared with sh-NC group. Conclusion DUXAP8 acted as a sponge of tumor suppressor miR-384 and then upregulated POU2F1 expression, thereby promoted the development of laryngeal cancer. Our findings suggest that DUXAP8 may serve as a potential therapeutic target for laryngeal cancer.

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ANRIL promotes chemoresistance via disturbing expression of ABCC1 by regulating the expression of Let-7a in colorectal cancer

Bioscience Reports ◽

10.1042/bsr20180620 ◽

2018 ◽

Vol 38 (6) ◽

Cited By ~ 16

Author(s):

Zhen Zhang ◽

Lifeng Feng ◽

Pengfei Liu ◽

Wei Duan

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Clinical Prognosis ◽

Normal Tissues ◽

Kaplan Meier ◽

Non Coding Rna ◽

Tumor Tissues ◽

Oncogenic Gene ◽

Poor Clinical Prognosis

Increasing evidence indicates that long non-coding RNAs (lncRNAs) antisense non-coding RNA in the INK4 locus (ANRIL) has been involved in various diseases and promotes tumorigenesis and cancer progression as an oncogenic gene. However, the effect of ANRIL on chemoresistance remains still unknown in colorectal cancer (CRC). Here, we investigated ANRIL expression in 63 cases of colorectal cancer specimens and matched normal tissues. Results revealed that ANRIL was up-regulated in tumor tissues samples from patients with CRC and CRC cell lines. Increased ANRIL expression in CRC was associated with poor clinical prognosis. Kaplan–Meier analysis showed that ANRIL was associated with overall survival of patients with colorectal cancer, and patients with high ANRIL expression tended to have unfavorable outcome. In vitro experiments revealed that ANRIL knockdown significantly inhibited CRC cell proliferation, improved the sensitivity of chemotherapy and promoted apoptosis. Further functional assays indicated that ANRIL overexpression significantly promoted cell chemoresistance by regulating ATP-binding cassette subfamily C member 1 through binding Let-7a. Taken together, our study demonstrates that ANRIL could act as a functional oncogene in CRC, as well as a potential therapeutic target to inhibit CRC chemoresistance.

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MiR-137 Suppresses Triple-Negative Breast Cancer Stemness and Tumorigenesis by Perturbing BCL11A-DNMT1 Interaction

Cellular Physiology and Biochemistry ◽

10.1159/000491526 ◽

2018 ◽

Vol 47 (5) ◽

pp. 2147-2158 ◽

Cited By ~ 18

Author(s):

Feiyu Chen ◽

Na Luo ◽

Yu Hu ◽

Xin Li ◽

Kejing Zhang

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Cell Lines ◽

Tumor Development ◽

Cancer Stemness ◽

Normal Tissues ◽

Tumor Tissues

Background/Aims: Triple negative breast cancer (TNBC) is resistant to conventional chemotherapy due to high proportions of cancer stem cells (CSCs). The aim of this study is to unravel the miR-137-mediated regulatory mechanism of B-cell lymphoma/leukemia 11A (BCL11A) in TNBC. Methods: A corhort of 34 TNBC tumor tissues and paired adjacent normal tissues, as well as 25 non-TNBC tumor tissues and paired adjacent normal tissues were collected post-operatively from patients with breast cancer. Q-PCR was performed to determine the mRNA levels of miR-137 and BCL11A in breast tissues and cell lines. Bioinformatics analysis and dual luciferase reporter assay were used to verify the direct interaction between miR-137 and BCL11A. After up-/down-regulation of BCL11A, miR-137, or DNMT1 via lentiviral transduction in TNBC cell lines SUM149 and MDA-MB-231 cells, Q-PCR and Western blot assays were used to detect the expression levels of BCL11A, DNA methyltransferases 1 (DNMT1), and Islet-1 (ISL1). Mammosphere assay was conducted to assess tumorosphere formation ability of cells, coupled with flow cytometry to determine the percentage of breast cancer stem cells. Co-immunoprecipitation assay was used to determine the interaction between BCL11A and DNMT1. Xenograft tumorigenesis assay was performed to monitor tumor formation in vivo. Results: BCL11A was highly expressed in TNBC, whereas miR-137 was significantly lower in both TNBC tissues and cell lines. miR-137 suppressed BCL11A expression at both mRNA and protein levels by directly targeting its 3’UTR. In both SUM149 and MDA-MB-231 cells, overexpression of miR-137 or knockdown of BCL11A reduced the number of tumoroshperes and the percentage of cancer stem cells in vitro, and inhibited tumor development in vivo. Furthermore, BCL11A interacted with DNMT1 in TNBC cells. Silencing of either BCL11A or DNMT1 impaired cancer stemness and tumorigenesis of TNBC via suppressing ISL1 expression both in vitro, and in vivo. Conclusions: By perturbing BCL11A-DNMT1 interaction, miR-137 impairs cancer stemness and suppresses tumor development in TNBC.

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TRIM39 deficiency inhibits tumor progression and autophagic flux in colorectal cancer via suppressing the activity of Rab7

Cell Death and Disease ◽

10.1038/s41419-021-03670-3 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Jia Hu ◽

Xueliang Ding ◽

Shaobo Tian ◽

Yanan Chu ◽

Zhibo Liu ◽

...

Keyword(s):

Colorectal Cancer ◽

Autophagic Flux ◽

Dependent Manner ◽

Functional Studies ◽

Normal Tissues ◽

Tumor Tissues ◽

Autophagic Degradation ◽

Activity Dependent

AbstractThe biological function of TRIM39, a member of TRIM family, remains largely unexplored in cancer, especially in colorectal cancer (CRC). In this study, we show that TRIM39 is upregulated in tumor tissues compared to adjacent normal tissues and associated with poor prognosis in CRC. Functional studies demonstrate that TRIM39 deficiency restrains CRC progression in vitro and in vivo. Our results further find that TRIM39 is a positive regulator of autophagosome–lysosome fusion. Mechanistically, TRIM39 interacts with Rab7 and promotes its activity via inhibiting its ubiquitination at lysine 191 residue. Depletion of TRIM39 inhibits CRC progression and autophagic flux in a Rab7 activity-dependent manner. Moreover, TRIM39 deficiency suppresses CRC progression through inhibiting autophagic degradation of p53. Thus, our findings uncover the roles as well as the relevant mechanisms of TRIM39 in CRC and establish a functional relationship between autophagy and CRC progression, which may provide promising approaches for the treatment of CRC.

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AVL9 promotes colorectal carcinoma cell migration via regulating EGFR expression

Biological Procedures Online ◽

10.1186/s12575-021-00162-8 ◽

2022 ◽

Vol 24 (1) ◽

Author(s):

Qiong Wu ◽

Jing De Chen ◽

Zhuqing Zhou

Keyword(s):

Cell Migration ◽

Colorectal Carcinoma ◽

Vital Role ◽

Protein Levels ◽

Normal Tissues ◽

Egfr Expression ◽

Tumor Tissues ◽

Potential Biomarker ◽

Proliferation In Vitro

Abstract Background Despite advanced treatments could inhibit progression of colorectal carcinoma (CRC), the recurrence and metastasis remain challenging issues. Accumulating evidences implicated that AVL9 played a vital role in human cancers, but it’s biological function and mechanism in CRC remain unclear. Aim To investigate the biological role and mechanism of AVL9 in colorectal carcinoma. Results AVL9 expression was significantly upregulated in tumor tissues than that in matched normal tissues both at mRNA and protein levels. High expression of AVL9 was closely correlated with M status, stages and poor prognosis of colorectal carcinoma (CRC) patients. Functionally, AVL9 overexpression promoted cell migration rather than cell proliferation in vitro, whereas AVL9 knockdown exhibited the contrary results. Mechanistically, AVL9 regulated EGFR expression, and knockdown of EGFR restrained AVL9-induced cell migration. Conclusion These findings demonstrated that AVL9 contributed to CRC cell migration by regulating EGFR expression, suggesting a potential biomarker and treatment target for CRC.

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Circ_0001955 facilitates hepatocellular carcinoma (HCC) tumorigenesis by sponging miR-516a-5p to release TRAF6 and MAPK11

Cell Death and Disease ◽

10.1038/s41419-019-2176-y ◽

2019 ◽

Vol 10 (12) ◽

Cited By ~ 21

Author(s):

Zhicheng Yao ◽

Ruiyun Xu ◽

Lin Yuan ◽

Mingxing Xu ◽

Haiyun Zhuang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Opposite Effect ◽

Target Genes ◽

Circular Rnas ◽

Rna Molecules ◽

Normal Tissues ◽

Tumor Tissues

AbstractCircular RNAs (circRNAs) have been increasingly demonstrated to function as novel promising therapeutic RNA molecules for diverse human diseases, including cancer. Although the important role of circRNAs has been well documented in HCC, the complex mechanisms of circRNAs in HCC need to be elucidated. Here, a novel circRNA circ_0001955 was identified from three GSE datasets (GSE7852, GSE94508, and GSE97322) as a differentially expressed circRNA between HCC and normal samples. We revealed that circ_0001955, TRAF6 and MAPK11 levels were increased, while miR-516a-5p levels were decreased in HCC tumor tissues compared to adjacent normal tissues. Knockdown of circ_0001955 repressed HCC tumor growth in vitro and in vivo, while overexpression of circ_0001955 exhibited the opposite effect. Circ_0001955 was identified as a sponge for miR-145-5p and miR-516a-5p, and TRAF6 and MAPK11 were demonstrated to be two target genes of miR-516a-5p. In conclusion, circ_0001955 facilitated HCC tumorigenesis by sponging miR-516a-5p to release TRAF6 and MAPK11 expression.

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AVL9 Promotes Colorectal Carcinoma Cell Migration via Regulating EGFR Expression

10.21203/rs.3.rs-952489/v1 ◽

2021 ◽

Author(s):

Qiong Wu ◽

JingDe Chen ◽

Zhuqing Zhou

Keyword(s):

Cell Migration ◽

Colorectal Carcinoma ◽

Vital Role ◽

Protein Levels ◽

Normal Tissues ◽

Egfr Expression ◽

Tumor Tissues ◽

Potential Biomarker ◽

Proliferation In Vitro

Abstract Background: Despite advanced treatments could inhibit progression of colorectal carcinoma (CRC), the recurrence and metastasis remain challenging issues. Accumulating evidences implicated that AVL9 played a vital role in human cancers, but it’s biological function and mechanism in CRC remain unclear.Aim: To investigate the biological role and mechanism of AVL9 in colorectal carcinoma.Results: AVL9 expression was significantly upregulated in tumor tissues than that in matched normal tissues both at mRNA and protein levels. High expression of AVL9 was closely correlated with M status, stages and poor prognosis of colorectal carcinoma (CRC) patients. Functionally, AVL9 overexpression promoted cell migration rather than cell proliferation in vitro, whereas AVL9 knockdown exhibited the contrary results. Mechanistically, AVL9 regulated EGFR expression, and knockdown of EGFR restrained AVL9-induced cell migration.Conclusion: These findings demonstrated that AVL9 contributed to CRC cell migration by regulating EGFR expression, implying a potential biomarker for CRC early diagnosis.

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miR-365 Suppresses Cholangiocarcinoma Cell Proliferation and Induces Apoptosis by Targeting E2F2

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504018x15188352857437 ◽

2018 ◽

Vol 26 (9) ◽

pp. 1375-1382 ◽

Cited By ~ 1

Author(s):

Lunjian Chen ◽

Xiaorong Huang ◽

Xinxin Chen

Keyword(s):

Cell Proliferation ◽

Inverse Correlation ◽

Normal Tissues ◽

Tumor Tissues ◽

Cholangiocarcinoma Cell ◽

Cellular Apoptosis ◽

Growth Of Tumor

Cholangiocarcinoma (CCA) is one of the most malignant adenocarcinomas arising from bile duct epithelial cells. However, the molecular mechanism regulating CCA development and progression still needs to be investigated. Here we found that miR-365 was downregulated in CCA tissues compared with adjacent normal tissues. By functional experiments, we found that overexpression of miR-365 significantly inhibited CCA cell proliferation and promoted cellular apoptosis in vitro. Furthermore, administration with miR-365 markedly suppressed the growth of tumor tissues in vivo. Mechanistically, we identified E2F2 as the target gene of miR-365 in CCA cells. We found that overexpression significantly inhibited the expression of E2F2 in CCA cells, and there was an inverse correlation between the expression levels of E2F2 and miR-365 in CCA tissues. We also found that E2F2 was highly expressed in CCA tissues and cell lines. Restoration of E2F2 in miR-365-overexpressing CCA cells promoted cell viability and reduced cellular apoptosis in CCA. Collectively, our study demonstrated the essential role of miR-365 and its functional mechanism in CCA cells, which provided a new insight on the design of therapeutic targets for CCA treatment.

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