Dataset Information

PRKRA promotes pancreatic cancer progression by upregulating MMP1 transcription via the NF-κB pathway.

ABSTRACT:

Objective

Pancreatic cancer (PC) is highly malignant, but the underlying mechanisms of cancer progression remain unclear. PRKRA is involved in cellular stress response, but its role in PC was unknown.

Methods

The expression of PRKRA between normal and tumor tissues were compared, and the prognostic value of PRKRA was evaluated. SiRNA and plasmids were applied to investigate the effects of PRKRA on PC cells. Organoids and cell lines with knockout and overexpression of PRKRA were established by CRISPR/Cas9 and lentivirus. The effects of PRKRA on PC were evaluated in vivo by cell-derived xenografts. The downstream genes of PRKRA were screened by transcriptome sequencing. The regulation of the target gene was validated by RT-qPCR, western blot, ChIP and dual luciferase reporter assay. Besides, the correlation between PRKRA and gemcitabine sensitivity was investigated by PC organoids.

Results

PRKRA was significantly overexpressed in PC tissues and independently associated with poor prognosis. PRKRA promoted the proliferation, migration, and chemoresistance of PC cells. The proliferation of PC organoids was decreased by PRKRA knockout. The growth and chemoresistance of xenografts were increased by PRKRA overexpression. Mechanistically, PRKRA upregulated the transcription of MMP1 via NF-κB pathway. ChIP and dual luciferase reporter assay showed that NF-κB subunit P65 could bind to the promoter of MMP1. The sensitivity of PC organoids to gemcitabine was negatively correlated with the expression of PRKRA and MMP1.

Conclusions

Our study indicated that the PRKRA/NF-κB/MMP1 axis promoted the progression of PC and may serve as a potential therapeutic target and prognosis marker.

SUBMITTER: Qiu J

PROVIDER: S-EPMC10361375 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

PRKRA promotes pancreatic cancer progression by upregulating MMP1 transcription via the NF-κB pathway.

Qiu Jiangdong J Feng Mengyu M Yang Gang G Su Dan D Zhao Fangyu F Liu Yueze Y Tao Jinxin J Luo Wenhao W Zhang Taiping T

Heliyon 20230610 6

<h4>Objective</h4>Pancreatic cancer (PC) is highly malignant, but the underlying mechanisms of cancer progression remain unclear. PRKRA is involved in cellular stress response, but its role in PC was unknown.<h4>Methods</h4>The expression of PRKRA between normal and tumor tissues were compared, and the prognostic value of PRKRA was evaluated. SiRNA and plasmids were applied to investigate the effects of PRKRA on PC cells. Organoids and cell lines with knockout and overexpression of PRKRA were es ...[more]

PMID: 37484321

Similar Datasets

Project description:Hepatocellular carcinoma (HCC) is a common malignant tumor that is characterized by aggressiveness and poor prognosis. Accumulating evidence indicates that oxidative stress plays a crucial role in carcinogenesis, whereas the potential mechanism between oxidative stress and carcinogenic effects remains elusive. In recent years, long noncoding RNAs (lncRNAs) in cancers have attracted extensive attention and have been shown to be involved in oxidative stress response and carcinogenesis. Nevertheless, the roles of lncRNA AL033381.2 in regulating the development and progression of HCC still remain unclear. The purpose of our study was to evaluate the potential effects and molecular mechanisms of AL033381.2 that may be involved in oxidative stress response in HCC. Using bioinformatics analyses based on the TCGA database, we screened and identified a novel lncRNA AL033381.2 in HCC, which may be involved in oxidative stress responses. qRT-PCR analysis revealed that AL033381.2 is upregulated in HCC tissues. Through in vitro and in vivo experiments, we found that AL033381.2 dramatically facilitates the growth and metastasis of HCC. Mechanistically, RNA pull-down experiments, mass spectrometry, PathArray™, and RIP were used to determine that AL033381.2 binds to PRKRA and may be involved in AL033381.2-mediated oncogenic functions in HCC cells. Moreover, rescue experiments demonstrated that PRKRA overexpression rescues the abilities of HCC cell proliferation, migration, and invasion that were affected by AL033381.2 knockdown. Furthermore, we produced a nanoparticle-based siRNA delivery system and tested its therapeutic effects in vivo. The results showed that the in vivo growth rate of the tumors treated with the nanoparticle/AL033381.2 siRNA complexes was dramatically lower than those treated with the nanoparticle/scramble siRNA complexes. Taken together, our results suggest that the novel lncRNA AL033381.2 may be involved in oxidative stress response by targeting oxidative stress-related genes in HCC. AL033381.2 plays vital oncogenic roles in HCC progression and may be a novel therapeutic marker for HCC diagnosis and treatment.

Dataset Information

PRKRA promotes pancreatic cancer progression by upregulating MMP1 transcription via the NF-κB pathway.

Objective

Methods

Results

Conclusions

Publications

PRKRA promotes pancreatic cancer progression by upregulating MMP1 transcription via the NF-κB pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets