Cucurbitacin E Inhibits Huh7 Hepatoma Carcinoma Cell Proliferation and Metastasis via Suppressing MAPKs and JAK/STAT3 Pathways

Cucurbitacin E (CuE), a highly oxygenated tetracyclic triterpene from Cucurbitaceae, has shown to exhibit potent cytotoxic and anti-proliferative properties against several human cancer cells. However, the underlying effects and mechanisms of CuE regarding hepatocellular carcinoma (HCC) have not been well understood. In the current study, unbiased RNA-sequencing (RNA-seq) and bioinformatics analysis was applied to elucidate the underlying molecular mechanism. CuE could significantly inhibit cell proliferation and migration of Huh7 cells, meanwhile CuE exhibited potent anti-angiogenic activity. RNA-seq analysis revealed that CuE negatively regulated 241 differentially expressed genes (DEGs) involved in multiple processes including cytoskeleton formation, angiogenesis and focal adhesion. Further analysis revealed that CuE effectually regulated diversified pharmacological signaling pathways such as MAPKs and JAK-STAT3. Our findings demonstrated the role of CuE in inhibiting proliferation and migration, providing an insight into the regulation of multiple signaling pathways as a new paradigm for anti-cancer treatment strategy.

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Long non-coding RNA LINC00152 regulates cell proliferation and migration by epigenetically repressing LRIG1 expression in cholangiocarcinoma

10.21203/rs.3.rs-76993/v1 ◽

2020 ◽

Author(s):

Ni Wang ◽

Yang Yu ◽

Boming Xu ◽

Chunmei Zhang ◽

Jie Liu ◽

...

Keyword(s):

Cell Proliferation ◽

Biological Function ◽

Rna Seq ◽

Normal Tissues ◽

Qrt Pcr ◽

Non Coding Rna ◽

And Migration ◽

Long Non Coding Rna ◽

Proliferation And Migration

Abstract Background: Recently, long non-coding RNAs (lncRNAs) have been verified to have significant regulatory roles in multiple human cancer processes. Long non-coding RNA LINC00152, located on chromosome 2p11.2, was identified as an oncogenic lncRNA in various cancers. However, the biological function and molecular mechanism of LINC00152 in cholangiocarcinoma (CCA) are still unknown.Methods: Bioinformatic analysis was performed to determine LINC00152 expression levels in the CCA and normal tissues by using raw microarray data downloaded from Gene Expression Omnibus (GSE76297) and The Cancer Genome Atlas (TCGA). Quantitative reverse transcription PCR (qRT-PCR) was used to validate LINC00152 expression in the CCA tissues compared with that in the paired normal tissues. CCK8, colony formation, Edu assays, transwell assays, flow cytometry, and in vivo tumor formation assays were performed to investigate the biological function of LINC00152 on CCA cell phenotypes. RNA-seq was carried out to identify the downstream target gene which was further examined by qRT-PCR, western bolt and rescue experiments. RNA immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assays were performed to reveal the factors involved in the mechanism of LINC00152 functions in CCA.Results: LINC00152 is significantly upregulated in cholangiocarcinoma. LINC00152 regulated the proliferation and migration of cholangiocarcinoma cells both in vitro and in vivo. RNA-seq revealed that LINC00152 knockdown preferentially affected genes linked with cell proliferation, cell differentiation and cell adhesion. Furthermore, mechanistic investigation validated that LINC00152 could bind EZH2 and modulate the histone methylation of promoter of leucine rich repeats and immunoglobulin like domains 1 (LRIG1), thereby affecting cholangiocarcinoma cells growth and migration.Conclusion: Taken together, these results demonstrated the significant roles of LINC00152 in cholangiocarcinoma and suggested a new diagnostic and therapeutic direction of cholangiocarcinoma.

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DOX-Vit D, a Novel Doxorubicin Delivery Approach, Inhibits Human Osteosarcoma Cell Proliferation by Inducing Apoptosis While Inhibiting Akt and mTOR Signaling Pathways

Pharmaceutics ◽

10.3390/pharmaceutics10030144 ◽

2018 ◽

Vol 10 (3) ◽

pp. 144 ◽

Cited By ~ 7

Author(s):

Zaid Maayah ◽

Ti Zhang ◽

Marcus Forrest ◽

Samaa Alrushaid ◽

Michael Doschak ◽

...

Keyword(s):

Cell Proliferation ◽

Cancer Cells ◽

Signaling Pathways ◽

Human Cancer ◽

Death Receptor ◽

Osteosarcoma Cell ◽

Acquired Drug Resistance ◽

Human Cancer Cells ◽

Mg63 Cells ◽

Delivery Approach

Doxorubicin (DOX) is a very potent and effective anticancer agent. However, the effectiveness of DOX in osteosarcoma is usually limited by the acquired drug resistance. Recently, Vitamin D (Vit-D) was shown to suppress the growth of many human cancer cells. Taken together, we synthesized DOX-Vit D by conjugating Vit-D to DOX in order to increase the delivery of DOX into cancer cells and mitigate the chemoresistance associated with DOX. For this purpose, MG63 cells were treated with 10 µM DOX or DOX-Vit D for 24 h. Thereafter, MTT, real-time PCR and western blot analysis were used to determine cell proliferation, genes and proteins expression, respectively. Our results showed that DOX-Vit D, but not DOX, significantly elicited an apoptotic signal in MG63 cells as evidenced by induction of death receptor, Caspase-3 and BCLxs genes. Mechanistically, the DOX-Vit D-induced apoptogens were credited to the activation of p-JNK and p-p38 signaling pathway and the inhibition of proliferative proteins, p-Akt and p-mTOR. Our findings propose that DOX-Vit D suppressed the growth of MG63 cells by inducing apoptosis while inhibiting cell survival and proliferative signaling pathways. DOX-Vit D may serve as a novel drug delivery approach to potentiate the delivery of DOX into cancer cells.

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Down-regulated Long Noncoding RNAHOXA11-ASaffects trophoblast cell proliferation and migration by regulatingRND3andHOXA7expression in preeclampsia

10.1101/285643 ◽

2018 ◽

Author(s):

Yetao Xu ◽

Dan Wu ◽

Jie Liu ◽

Zhonghua Ma ◽

Bingqing Hui ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Growth ◽

Noncoding Rna ◽

Trophoblast Cell ◽

Rna Seq ◽

Biological Mechanisms ◽

Aberrant Expression ◽

Cell Growth And Migration ◽

And Migration ◽

Proliferation And Migration

AbstractThe long noncoding RNAHOXA11-ASreveals abnormal expression in numerous human diseases. However, its function and biological mechanisms remain unclear in Preeclampsia (PE). In this study, we report thatHOXA11-ASwas significantly downregulated in preeclampsic placental tissues and could contribute to the occurrence and development of Preeclampsia. Silencing ofHOXA11-ASexpression could significantly suppress trophoblast cell growth and migration, whereasHOXA11-ASoverexpression facilitated cell growth in HTR-8/SVneo, JEG3 and JAR cell lines. RNA-seq analysis also indicated thatHOXA11-ASsilencing preferentially regulated numerous genes associated with cell proliferation and cell migration. Mechanistic analyses showed thatHOXA11-AScould recruit Ezh2 and Lsd1 protein, and regulateRND3mRNA expression in nucleus. In cytoplasm,HOXA11-ASmodulateHOXA7expression by sponged miR-15b-5p, thus affecting trophoblast cell proliferation. Together, these resulting data confirm that aberrant expression ofHOXA11-ASis involved in the occurrence and development of Preeclampsia, and may act as a prospective diagnosis and therapeutic target in PE.

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Differential effects of platelet-derived growth factor isotypes on human smooth muscle cell proliferation and migration are mediated by distinct signaling pathways

Surgery ◽

10.1016/s0039-6060(96)80319-9 ◽

1996 ◽

Vol 120 (2) ◽

pp. 427-432 ◽

Cited By ~ 46

Author(s):

Baoen Jiang ◽

Shinji Yamamura ◽

Peter R. Nelson ◽

Leila Mureebe ◽

K. Craig Kent

Keyword(s):

Cell Proliferation ◽

Smooth Muscle ◽

Growth Factor ◽

Smooth Muscle Cell ◽

Signaling Pathways ◽

Platelet Derived Growth Factor ◽

Cell Proliferation And Migration ◽

Human Smooth Muscle Cell ◽

And Migration ◽

Proliferation And Migration

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MiR-186-3p attenuates tumorigenesis of cervical cancer by targeting IGF1

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02317-z ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Xiurong Lu ◽

Xiao Song ◽

Xiaohui Hao ◽

Xiaoyu Liu ◽

Xianyu Zhang ◽

...

Keyword(s):

Cervical Cancer ◽

Human Cancer ◽

Luciferase Reporter ◽

Inhibitory Effects ◽

Protein Coding ◽

Human Cancer Cells ◽

And Migration ◽

Igf1 Expression ◽

Gene Expression Levels ◽

Proliferation And Migration

Abstract Background Mounting evidence in the cancer literature suggests that microRNAs (miRNAs) influence the progression of human cancer cells by targeting protein-coding genes. How insulin-like growth factor 1(IGF1) and miR-186-3p contribute to the development of cervical cancer (CC) remains unclear. This study examined the regulatory roles of miR-186-3p and IGF1 in CC development. Methods Gene expression levels were determined by qRT-PCR. Proliferation, migration, and apoptosis of CC and normal cells were determined by MTT, Transwell, and caspase-3 activity assays, respectively. Dual-luciferase reporter activity and RNA pull-down assays were performed to identify the target gene of miR-186-3p. Results IGF1 was the target of miR-186-3p. The expression of miR-186-3p inhibited cell proliferation and migration abilities of CC cell lines, but induced the apoptosis rate of CC cells. IGF1 could restore the inhibitory effects of miR-186-3p on the proliferation, migration, and apoptosis abilities of CC cells. Experimental results revealed that miR-186-3p could inhibit IGF1 expression, thereby reducing the viability of CC cells. Conclusions The data suggest that targeting of IGF1 by miR-186-3p could be crucial in regulating the progression of CC.

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TMEM176B Regulates AKT/mTOR Signaling and Tumor Growth in Triple-Negative Breast Cancer

Cells ◽

10.3390/cells10123430 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3430

Author(s):

Chifei Kang ◽

Ran Rostoker ◽

Sarit Ben-Shumel ◽

Rola Rashed ◽

James Andrew Duty ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cell Proliferation ◽

Tumor Growth ◽

Signaling Pathways ◽

Cancer Cell ◽

And Migration ◽

Proliferation And Migration

TMEM176B is a member of the membrane spanning 4-domains (MS4) family of transmembrane proteins, and a putative ion channel that is expressed in immune cells and certain cancers. We aimed to understand the role of TMEM176B in cancer cell signaling, gene expression, cell proliferation, and migration in vitro, as well as tumor growth in vivo. We generated breast cancer cell lines with overexpressed and silenced TMEM176B, and a therapeutic antibody targeting TMEM176B. Proliferation and migration assays were performed in vitro, and tumor growth was evaluated in vivo. We performed gene expression and Western blot analyses to identify the most differentially regulated genes and signaling pathways in cells with TMEM176B overexpression and silencing. Silencing TMEM176B or inhibiting it with a therapeutic antibody impaired cell proliferation, while overexpression increased proliferation in vitro. Syngeneic and xenograft tumor studies revealed the attenuated growth of tumors with TMEM176B gene silencing compared with controls. We found that the AKT/mTOR signaling pathway was activated or repressed in cells overexpressing or silenced for TMEM176B, respectively. Overall, our results suggest that TMEM176B expression in breast cancer cells regulates key signaling pathways and genes that contribute to cancer cell growth and progression, and is a potential target for therapeutic antibodies.

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