LncRNA SNHG7 promotes pancreatic cancer proliferation through ID4 by sponging miR-342-3p

Mind bomb 1 (MIB1), an E3 ligase, plays a vital role in chemo-resistance and cancer metastasis. According to The Cancer Genome Atlas (TCGA), MIB1 gene is preferentially amplified in pancreatic cancer. Copy number alterations in MIB1 gene are associated with worse survival. Gene Expression Omnibus (GEO) also showed that pancreatic cancer with high mRNA level of MIB1 tend to be more resistant to gemcitabine and higher mRNA levels of MIB1 are found in pancreatic tumors compared with adjacent normal tissues. MIB1 knockdown (KD) in Panc-1 and HPAF2 cell lines significantly inhibit proliferation and colony formation of pancreatic cancer. The gene set enrichment analysis (GSEA) has also showed that β-catenin is the downstream of MIB1. Western blot analysis showed that total and active β-catenin levels are decreased in MIB1 KD cells. β-catenin inhibitor also inhibits proliferation of Panc-1 and HPAF2 cells. We in this study implanted HPAF2 scramble and MIB1 KD cells orthotopically in athymic nude mice. Gemcitabine was used to treat the mice. Results revealed that after MIB1 KD HPAF2 cells were more sensitive to gemcitabine. In conclusion, we demonstrated that MIB1 promotes pancreatic cancer proliferation through activating β-catenin signaling. MIB1 may thus be a therapeutic target in pancreatic cancer therapy.

Download Full-text

Adipocytes Promote Pancreatic Cancer Proliferation via a Hepatocyte Growth Factor-Mediated Mechanism

Journal of Surgical Research ◽

10.1016/j.jss.2009.11.059 ◽

2010 ◽

Vol 158 (2) ◽

pp. 187-188

Author(s):

K.M. Dalbec ◽

R.V. Considine ◽

S. Wang ◽

D.A. Swartz-Basile ◽

H.A. Pitt ◽

...

Keyword(s):

Pancreatic Cancer ◽

Growth Factor ◽

Hepatocyte Growth Factor ◽

Cancer Proliferation ◽

Hepatocyte Growth

Download Full-text

CircSEC24A upregulates TGFBR2 expression to accelerate pancreatic cancer proliferation and migration via sponging to miR-606

Cancer Cell International ◽

10.1186/s12935-021-02392-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yankun Chen ◽

Simiao Xu ◽

Xinyuan Liu ◽

Xueyi Jiang ◽

Jianxin Jiang

Keyword(s):

Pancreatic Cancer ◽

Cell Lines ◽

Circular Rna ◽

Luciferase Reporter ◽

Cancer Proliferation ◽

Diagnosis And Prognosis ◽

Pancreatic Cancer Cells ◽

Invasive Capacity ◽

And Migration ◽

Cancer Tissues

Abstract Background Circular RNA (circRNA), producing by special selective splicing, was widely expressed in the cytoplasm of eukaryotic cells as a newly non-coding RNAs. It played different roles in a variety of diseases including cancer and performed different functions. Nonetheless, reports on the specific function of circRNA in pancreatic cancer (PC) were still rarely so far. In particular, the role of circSEC24A in PC remains unclear. Methods Real-time fluorescent quantitative PCR was used to evaluate the expression level of circSEC24A in pancreatic cancer tissues and cell lines. Furthermore, we used some functional experiments, such as EDU and Transwell assays, to explore the effects of circSEC24A on the proliferation and invasiveness of pancreatic cancer. Finally, the corresponding relationship among circSEC24A, miR-606 and TGFBR2 was explored by dual luciferase reporter and other mechanism studies. Results The expression of circSEC24A in both pancreatic cancer tissues and cell lines was evidently up-regulated. Furthermore, knockdown of circSEC24A significantly inhibited the proliferative, migration and invasive capacity of pancreatic cancer cells, whereas miR-606 inhibitor obviously counteracted these effects. Further study confirmed that circSEC24A alleviated suppression on target TGFBR2 expression by directly sponging miR-606 and then influenced the tumorigenesis of pancreatic cancer. Conclusions These findings indicated that the progression of pancreatic cancer can be driven by circSEC24A influencing miR-606/TGFBR2 axis. Therefore, circSEC24A might be used as a critical biomarker influencing the early diagnosis and prognosis of pancreatic cancer.

Download Full-text

Isoalantolactone inhibits pancreatic cancer proliferation by regulation of PI3K and Wnt signal pathway

PLoS ONE ◽

10.1371/journal.pone.0247752 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0247752

Author(s):

Chaoxiong Zhang ◽

Lei Huang ◽

Jingyuan Xiong ◽

Linshen Xie ◽

Shi Ying ◽

...

Keyword(s):

Pancreatic Cancer ◽

Pancreatic Adenocarcinoma ◽

Cell Lines ◽

Signal Pathway ◽

Cancer Proliferation ◽

Adenocarcinoma Cell ◽

Wnt Signal Pathway ◽

Canonical Wnt ◽

Wnt Signal

Background/aims Isoalantolactone (IATL) is one of multiple isomeric sesquiterpene lactones and is isolated from inula helenium. IATL has multiple functions such as antibacterial, antihelminthic and antiproliferative activities. IATL also inhibits pancreatic cancer proliferation and induces apoptosis by increasing ROS production. However, the detailed mechanism of IATL-mediated pancreatic cancer apoptosis remains largely unknown. Methods In current study, pancreatic carcinoma cell lines (PANC-1, AsPC-1, BxPC-3) and a mouse xenograft model were used to determine the mechanism of IATL-mediated toxic effects. Results IATL (20μM) inhibited pancreatic adenocarcinoma cell lines proliferation in a time-dependent way; while scratch assay showed that IATL significantly inhibited PANC-1 scratch closure (P<0.05); Invasion assays indicated that IATL significantly attenuated pancreatic adenocarcinoma cell lines invasion on matrigel. Signal analysis showed that IATL inhibited pancreatic adenocarcinoma cell proliferation by blocking EGF-PI3K-Skp2-Akt signal axis. Moreover, IATL induced pancreatic adenocarcinoma cell apoptosis by increasing cytosolic Caspase3 and Box expression. This apoptosis was mediated by inhibition of canonical wnt signal pathway. Finally, xenograft studies showed that IATL also significantly inhibited pancreatic adenocarcinoma cell proliferation and induced pancreatic adenocarcinoma cell apoptosis in vivo. Conclusions IATL inhibits pancreatic cancer proliferation and induces apoptosis on cellular and in vivo models. Signal pathway studies reveal that EGF-PI3K-Skp2-Akt signal axis and canonical wnt pathway are involved in IATL-mediated cellular proliferation inhibition and apoptosis. These studies indicate that IATL may provide a future potential therapy for pancreatic cancer.

Download Full-text

Hypoxia-Induced ZWINT Mediates Pancreatic Cancer Proliferation by Interacting With p53/p21

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.682131 ◽

2021 ◽

Vol 9 ◽

Author(s):

Peng Chen ◽

Zhiwei He ◽

Jie Wang ◽

Jian Xu ◽

Xueyi Jiang ◽

...

Keyword(s):

Cell Cycle ◽

Pancreatic Cancer ◽

Cell Cycle Progression ◽

Bioinformatic Analysis ◽

Vital Role ◽

Luciferase Assay ◽

Tissue Array ◽

Cancer Proliferation ◽

Mrna And Protein Expression ◽

P53 Activation

p53/p21 signaling plays a vital role in pancreatic cancer (PC) progression. ZWINT was shown to function as an oncoprotein in the progression of multiple cancers. However, the involvement of ZWINT and p53 activation in the progression of PC remains poorly understood. Bioinformatics and tissue array chip analyses were performed to evaluate ZWINT expression in pancreatic cancer. ZWINT mRNA and protein expression were evaluated in normoxia and hypoxia. CHIP was used to evaluate HIF1α interaction with the ZWINT promoter. CCK8, colony formation, EDU, and cell cycle analysis were used to examine PC cell proliferation. Immunoprecipitation and immunofluorescence were used to examine the interaction of ZWINT, MDM2, and p53. p53 activity was evaluated by q-PCR and luciferase assay. Protein degradation and ubiquitination assays were used to analyze the role of ZWINT in p53 ubiquitination. ZWINT was overexpressed in pancreatic cancer and induced in hypoxia. ZWINT promoted pancreatic cancer growth and cell cycle progression. Bioinformatic analysis revealed that ZWINT may regulate the p53 signal pathway. ZWINT interacts with p53 and promotes its ubiquitination and degradation. ZWINT promoted proliferation via p53/p21. Immunohistochemistry of clinical specimens revealed that that ZWINT expression was significantly negatively correlated with p53/p21. Our data showed that hypoxia regulates the expression of ZWINT, which activated p53/p21 signaling pathway to promote PC growth.

Download Full-text