TAT-Beclin1 Represses the Carcinogenesis of DUSP4-positive PTC by Enhancing Autophagy

Abstract Background: DUSP4 is a pro-tumorigenic molecule of papillary thyroid carcinoma (PTC). DUSP4 also exists as an autophagic regulator. Moreover, DUSP4, as a negative regulator of MAPK, can prevent Beclin1 from participating in autophagic response. This study aimed to explore whether TAT-Beclin1, a recombinant protein of Beclin1, could inhibit the tumorigenesis of DUSP4-positive PTC by regulating autophagy.Methods: First, we divided PTC cancer tissues into three groups according to DUSP4 expression levels by immunohistochemical analyses, and evaluated the relationship between the expression of autophagic proteins (Beclin1 and LC3II) and DUSP4 expression using Western blotting assays. After overexpression of DUSP4 by lentiviral transduction, the roles of TAT-Beclin1 on DUSP4-overexpressed PTC was detected.Results: Our results showed that the expression levels of autophagic proteins (Beclin1 and LC3II) increased with the increase of DUSP4 expression in PTC carcinomas. In PTC cells, DUSP4 overexpression-inhibited autophagic activity (including Beclin1 expression, LC3 conversion rate and LC3-puncta formation) and -promoted cell proliferation and migration were reversed by TAT-Beclin1 administration. In vivo assays also showed that DUSP4-overexpressed PTC cells had stronger tumorigenic ability and weaker autophagic activity, which was recovered by TAT-Beclin1 administration. Conclusions: TAT-Beclin1, as an autophagic promoter, could repress the carcinogenesis of DUSP4-positive PTC, which implies that the addition of TAT-Beclin1 may be determined through detecting the levels of DUSP4 in the treatment of PTC.

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MicroRNA-449a delays lung cancer development through inhibiting KDM3A/HIF-1α axis

Journal of Translational Medicine ◽

10.1186/s12967-021-02881-8 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Shan Hu ◽

Peng Cao ◽

Kangle Kong ◽

Peng Han ◽

Yu Deng ◽

...

Keyword(s):

Lung Cancer ◽

Cell Cycle ◽

Cellular Growth ◽

Cancer Development ◽

Invasion And Migration ◽

And Migration ◽

Cancer Tissues ◽

Lysine Demethylase ◽

The Relationship

Abstract Background It has been established that microRNA (miR)-449a is anti-tumorigenic in cancers, including lung cancer. Therefore, this study further explored miR-449a-mediated mechanism in lung cancer, mainly focusing on lysine demethylase 3A/hypoxia-induced factor-1α (KDM3A/HIF-1α) axis. Methods miR-449a, KDM3A and HIF-1α levels in lung cancer tissues and cell lines (A549, H1299 and H460) were measured. Loss- and gain-of-function assays were performed and then cell proliferation, cell cycle, apoptosis, invasion and migration were traced. The relationship between KDM3A, miR-449a and HIF-1α was verified. Tumor growth in vivo was also monitored. Results Both lung cancer tissues and cells exhibited reduced miR-449a and raised KDM3A and HIF-1α levels. miR-449a interacted with KDM3A; HIF-1α could bind with KDM3A. Up-regulating miR-449a hindered while suppressing miR-449a induced lung cancer development via mediating HIF-1α. Elevating KDM3A promoted cellular aggression while down-regulating KDM3A had the opposite effects. Up-regulating KDM3A or HIF-1α negated up-regulated miR-449a-induced effects on cellular growth in lung cancer. Restoring miR-449a impaired tumorigenesis in vivo in lung cancer. Conclusion It is eventually concluded that miR-449a delays lung cancer development through suppressing KDM3A/HIF-1α axis.

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RNA-sequencing identified miR-3681 as a negative regulator in the proliferation and migration of cervical cancer cells via the posttranscriptional suppression of HGFR

RSC Advances ◽

10.1039/c9ra01785b ◽

2019 ◽

Vol 9 (39) ◽

pp. 22376-22383 ◽

Cited By ~ 1

Author(s):

Fan Shi ◽

Yingbing Zhang ◽

Juan Wang ◽

Jin Su ◽

Zi Liu ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Rna Sequencing ◽

Negative Regulator ◽

Tumor Tissues ◽

Differentially Expressed Mirnas ◽

Cervical Cancer Cells ◽

And Migration ◽

Cancer Tissues ◽

Proliferation And Migration

In this study, RNA-sequencing was used to investigate the differentially expressed miRNAs between cervical cancer tissues and matched adjacent non-tumor tissues.

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AHA1 upregulates IDH1 and metabolic activity to promote growth and metastasis and predicts prognosis in osteosarcoma

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-020-00387-1 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Diwei Zheng ◽

Weihai Liu ◽

Wenlin Xie ◽

Guanyu Huang ◽

Qiwei Jiang ◽

...

Keyword(s):

Metabolic Activity ◽

Cancer Metabolism ◽

Cancer Metastasis ◽

Isocitrate Dehydrogenase 1 ◽

Cell Growth And Migration ◽

And Migration ◽

The Relationship ◽

Common Primary Malignant Bone

AbstractOsteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. Although activator of HSP90 ATPase activity 1 (AHA1) is reported to be a potential oncogene, its role in osteosarcoma progression remains largely unclear. Since metabolism reprogramming is involved in tumorigenesis and cancer metastasis, the relationship between AHA1 and cancer metabolism is unknown. In this study, we found that AHA1 is significantly overexpressed in osteosarcoma and related to the prognosis of osteosarcoma patients. AHA1 promotes the growth and metastasis of osteosarcoma both in vitro and in vivo. Mechanistically, AHA1 upregulates the metabolic activity to meet cellular bioenergetic needs in osteosarcoma. Notably, we identified that isocitrate dehydrogenase 1 (IDH1) is a novel client protein of Hsp90-AHA1. Furthermore, the IDH1 protein level was positively correlated with AHA1 in osteosarcoma. And IDH1 overexpression could partially reverse the effect of AHA1 knockdown on cell growth and migration of osteosarcoma. Moreover, high IDH1 level was also associated with poor prognosis of osteosarcoma patients. This study demonstrates that AHA1 positively regulates IDH1 and metabolic activity to promote osteosarcoma growth and metastasis, which provides novel prognostic biomarkers and promising therapeutic targets for osteosarcoma patients.

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GNG5 is a novel oncogene associated with cell migration, proliferation, and poor prognosis in glioma

10.21203/rs.3.rs-49192/v2 ◽

2021 ◽

Author(s):

Wang Zhang ◽

Zhendong Liu ◽

Binchao Liu ◽

Miaomiao Jiang ◽

Shi Yan ◽

...

Keyword(s):

Signaling Pathways ◽

Clinical Data ◽

Poor Prognosis ◽

Glioma Cells ◽

Diagnosis And Treatment ◽

And Migration ◽

The Relationship ◽

Proliferation And Migration

Abstract Background: Although many biomarkers have been reported for detecting glioma, the prognosis for the disease remains poor, and therefore, new biomarkers need to be identified. GNG5, which is part of the G-protein family, has been associated with different malignant tumors, though the role of GNG5 in glioma has not been studied. Therefore, we aimed to identify the relationship between GNG5 and glioma prognosis and identify a new biomarker for the diagnosis and treatment of gliomas.Methods: We used data on more than a thousand gliomas from multiple databases and clinical data to determine the expression of GNG5 in glioma. Based on clinical data and CGGA database, we identified the correlation between GNG5 and multiple molecular and clinical features and prognosis using various analytical methods. Co-expression analysis and GSEA were performed to detect GNG5-related genes in glioma and possible signaling pathways involved. ESTIMATE, ssGSEA, and TIMER were used to detect the relationship between GNG5 and the immune microenvironment. Functional experiments were performed to explore the function of GNG5 in glioma cells.Results: GNG5 is highly expressed in gliomas, and its expression level is positively correlated with pathological grade, histological type, age, and tumor recurrence and negatively correlated with isocitrate dehydrogenase mutation, 1p/19 co-deletion, and chemotherapy. Moreover, GNG5 as an independent risk factor was negatively correlated with the overall survival time. GSEA revealed the potential signaling pathways involved in GNG5 function in gliomas, including cell adhesion molecules signaling pathway. The ssGSEA, ESTIMATE, and TIMER based analysis indicated a correlation between GNG5 expression and various immune cells in glioma. In vivo and in vitro experiments showed that GNG5 could participate in glioma cell proliferation and migration.Conclusions: Based on the large data platform and the use of different databases to corroborate results obtained using various datasets, as well as in vitro and in vivo experiments, our study reveals for the first time that GNG5, as an oncogene, is overexpressed in gliomas and can inhibit the proliferation and migration of glioma cells and lead to poor prognosis of patients. Thus, GNG5 is a potential novel biomarker for the clinical diagnosis and treatment of gliomas.

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Chondroitin polymerizing factor (CHPF) promotes development of malignant melanoma through regulation of CDK1

Cell Death and Disease ◽

10.1038/s41419-020-2526-9 ◽

2020 ◽

Vol 11 (7) ◽

Author(s):

Wei Sun ◽

Fang Zhao ◽

Yu Xu ◽

Kai Huang ◽

Xianling Guo ◽

...

Keyword(s):

Malignant Melanoma ◽

Pathway Analysis ◽

Normal Skin ◽

Over Expression ◽

Tumor Promotor ◽

And Migration ◽

First Time ◽

The Relationship

Abstract Chondroitin polymerizing factor (CHPF) is an important member of glycosyltransferases involved in the biosynthesis of chondroitin sulfate (CS). However, the relationship between CHPF and malignant melanoma (MM) is still unknown. In this study, it was demonstrated that CHPF was up-regulated in MM tissues compared with the adjacent normal skin tissues and its high expression was correlated with more advanced T stage. Further investigations indicated that the over-expression/knockdown of CHPF could promote/inhibit proliferation, colony formation and migration of MM cells, while inhibiting/promoting cell apoptosis. Moreover, knockdown of CHPF could also suppress tumorigenicity of MM cells in vivo. RNA-sequencing followed by Ingenuity pathway analysis (IPA) was performed for exploring downstream of CHPF and identified CDK1 as the potential target. Furthermore, our study revealed that knockdown of CDK1 could inhibit development of MM in vitro, and alleviate the CHPF over-expression induced promotion of MM. In conclusion, our study showed, as the first time, CHPF as a tumor promotor for MM, whose function was carried out probably through the regulation of CDK1.

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Expression analysis and implication of Rab1A in gastrointestinal relevant tumor

Scientific Reports ◽

10.1038/s41598-019-49786-7 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Menglin Xu ◽

Xinyu Shao ◽

Xiaoyi Kuai ◽

Liping Zhang ◽

Chunli Zhou ◽

...

Keyword(s):

Strongly Correlated ◽

Gastrointestinal Cancers ◽

Gastrointestinal Tumor ◽

Expression Levels ◽

Promising Therapeutic Target ◽

Tumor Tissues ◽

Mtorc1 Pathway ◽

And Migration

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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Impact of protamine I on colon cancer proliferation, invasion, migration, diagnosis and prognosis

Biological Chemistry ◽

10.1515/hsz-2017-0222 ◽

2018 ◽

Vol 399 (3) ◽

pp. 265-275 ◽

Cited By ~ 1

Author(s):

Zhi Chen ◽

Chunyu Shi ◽

Shuohui Gao ◽

Defeng Song ◽

Ye Feng

Keyword(s):

Colon Cancer ◽

Cell Invasion ◽

Cell Apoptosis ◽

Xenograft Model ◽

Enzyme Linked Immunosorbent Assay ◽

Invasion And Migration ◽

Diagnosis And Prognosis ◽

And Migration ◽

Cancer Tissues

AbstractThis paper investigates protamine I (PRM1) expression and its effects on proliferation, invasion and migration of colon cancer cells as well as its function in clinical diagnosis and prognosis. Gene chips were used to screen differentially expressed genes. PRM1 expression was detected by Western blotting and quantitative real time-polymerase chain reaction (qRT-PCR). Hematoxylin and eosin (HE) staining and immunohistochemistry were utilized to compare the expression of PRM1 from multiple differentiation levels of colon cancer tissues. Cell viability, cell apoptosis and cell cycle were tested using the MTT assay and flow cytometry. Cell invasion and migration capability were tested using the Transwell assay and wound healing.In vivoeffects of PRM1 on colon cancer were explored using a xenograft model.PRM1expression in serum was detected by enzyme-linked immunosorbent assay (ELISA). The expression level of PRM1 was significantly higher in colon cancer tissues and the staining degree of PRM1 in poorly-differentiated was stronger. pcDNA3.1-PRM1 decreased cell apoptosis while it increased the proliferation, cell invasion and migration. The si-PRM1 group displayed an opposite tendency. The serum PRM1 level was significantly higher and could serve as a diagnostic biomarker for colon cancer.

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METTL3 promotes the initiation and metastasis of ovarian cancer by inhibiting CCNG2 expression via promoting the maturation of pri-microRNA-1246

Cell Death Discovery ◽

10.1038/s41420-021-00600-2 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Xuehan Bi ◽

Xiao Lv ◽

Dajiang Liu ◽

Hongtao Guo ◽

Guang Yao ◽

...

Keyword(s):

Ovarian Cancer ◽

Molecular Mechanisms ◽

High Expression ◽

Ovarian Cancer Cells ◽

Inadequate Knowledge ◽

And Migration ◽

Cancer Tissues

AbstractOvarian cancer is a common gynecological malignant tumor with a high mortality rate and poor prognosis. There is inadequate knowledge of the molecular mechanisms underlying ovarian cancer. We examined the expression of methyltransferase-like 3 (METTL3) in tumor specimens using RT-qPCR, immunohistochemistry, and Western blot analysis, and tested the methylation of METTL3 by MSP. Levels of METTL3, miR-1246, pri-miR-1246 and CCNG2 were then analyzed and their effects on cell biological processes were also investigated, using in vivo assay to validate the in vitro findings. METTL3 showed hypomethylation and high expression in ovarian cancer tissues and cells. Hypomethylation of METTL3 was pronounced in ovarian cancer samples, which was negatively associated with patient survival. Decreased METTL3 inhibited the proliferation and migration of ovarian cancer cells and promoted apoptosis, while METTL3 overexpression exerted opposite effects. Mechanistically, METTL3 aggravated ovarian cancer by targeting miR-1246, while miR-1246 targeted and inhibited CCNG2 expression. High expression of METTL3 downregulated CCNG2, promoted the metabolism and growth of transplanted tumors in nude mice, and inhibited apoptosis. The current study highlights the promoting role of METTL3 in the development of ovarian cancer, and presents new targets for its treatment.

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TM4SF1 Regulates Pancreatic Cancer Migration and Invasion In Vitro and In Vivo

Cellular Physiology and Biochemistry ◽

10.1159/000445664 ◽

2016 ◽

Vol 39 (2) ◽

pp. 740-750 ◽

Cited By ~ 19

Author(s):

Jia Cao ◽

Jia-chun Yang ◽

Vijaya Ramachandran ◽

Thiruvengadam Arumugam ◽

De-feng Deng ◽

...

Keyword(s):

Pancreatic Cancer ◽

Pancreatic Tumor ◽

Migration And Invasion ◽

Qrt Pcr ◽

Pancreatic Cancer Cells ◽

Cancer Tissues ◽

Immunohistochemical Analyses ◽

Expression And Activity

Background/Aims: The cell surface protein transmembrane 4 L6 family member 1 (TM4SF1) has been detected in various tumors and plays a major role in the development of cancer. We aimed to investigate the effects of TM4SF1 on the migration and invasion of pancreatic cancer in vitro and in vivo and explore its related molecular mechanisms. Methods: qRT-PCR and immunohistochemical analyses were used to measure the expression of TM4SF1 in pancreatic cancer tissues and adjacent tissues. TM4SF1 was silenced using siRNA and shRNA to investigate the role of this protein in the proliferation and metastasis of pancreatic cancer cells. MTS and Transwell assays were used to examine the effect of TM4SF1 on pancreatic cancer cell lines. The expression and activity of MMP-2 and MMP-9 were determined by qRT-PCR, western blots and gelatin zymography. In vivo, orthotopic pancreatic tumor models were used to examine the formation of metastasis. Results: qRT-PCR and immunohistochemical analyses showed that TM4SF1 was highly expressed in pancreatic cancer tissues compared with the adjacent tissues. In in vitro experiments the silencing of TM4SF1 reduced cell migration and invasion and down-regulated the expression and activity of MMP-2 and MMP-9. However, no significant difference in cell proliferation was detected after silencing TM4SF1. Additionally, knocking down TM4SF1 decreased the formation of lung and liver metastases in orthotopic pancreatic tumor models. Conclusion: Our results demonstrate that the expression of TM4SF1 is higher in pancreatic cancer tissues and pancreatic cancer cell lines than controls. Knockdown of TM4SF1 inhibited the migration and invasion of pancreatic cancer cells by regulating the expression and activity of MMP-2 and MMP-9, which suggests that TM4SF1 may play a significant role in metastasis in pancreatic cancer.

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miR-495-3p Depresses Cell Proliferation and Migration By Down-Regulating HMGB1 in Colorectal Cancer

10.21203/rs.3.rs-663678/v1 ◽

2021 ◽

Author(s):

Zhang Jieling ◽

Li Kai ◽

Zheng Huifen ◽

Zhu Yiping

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Luciferase Reporter ◽

Luciferase Reporter Gene ◽

Gene Assay ◽

And Migration ◽

Cancer Tissues

Abstract Background: MicroRNAs play an important role in the genesis and progression of tumors, including colorectal cancer (CRC), which has a high morbidity and mortality rate. In this research, the role of miR-495-3p and HMGB1 in CRC was investigated.Methods: We performed qRT-PCR to detect the expression of miR-495-3p in colorectal cancer tissues and cell lines. Functional experiments such as CCK-8 assay, EDU assay, Transwell assay and apoptosis assay were conducted to explore the effects of miR-495-3p on the proliferation, migration and apoptosis of CRC cells in vitro. Then, the use of database prediction, dual-luciferase reporter gene assay and functional experiments verified the role of miR-495-3p target gene HMGB1 in CRC. Finally, rescue experiments was performed to investigate whether overexpression of HMGB1 could reverse the inhibitory effect of miR-495-3p on CRC cell proliferation in vivo and in vitro.Results: miR-495-3p was down-regulated in colorectal cancer tissues and cell lines, and could inhibit the proliferation and migration of colorectal cancer cells, and promote cell apoptosis. The database prediction and dual-luciferase reporter gene assay showed that HMGB1 was the downstream target gene of miR-495-3p. We finally demonstrated that miR-495-3p inhibited CRC cell proliferation by targeting HMGB1 in vitro and in vivo.Conclusion: Our research shows that miR-495-3p inhibits the progression of colorectal cancer by down-regulating the expression of HMGB1, which indicates that miR-495-3p may become a potential therapeutic target for colorectal cancer.

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