Emerging role and function of miR-198 in human health and diseases

Kaushik, Pankhuri; Kumar, Arun

doi:10.1016/j.prp.2021.153741

Cited by 5 publications

(3 citation statements)

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“…MiR-198 is an exonic miRNA transcribed in the 3′UTR of Follistatin-like 1 ( FSTL1 ), which plays a role in wound healing [ 70 ]. It has also attracted a lot of attention as an integral tumor suppressive player in several cancers, where it targets several key factors involved in the complex tumorigenic regulatory network, and exogenous administration of miR-198 in vitro and in vivo leads to a reduction in proliferation, migration, and invasion in multiple cancer types; for a review, see [ 34 , 35 ]. Since VCP is a direct target of miR-198 [ 36 , 37 ], we examined whether exogenous administration of miR-198 could alter autophagy through VCP targeting and sensitize cancer cells to gemcitabine.…”

Section: Discussionmentioning

confidence: 99%

“…Our group and others found that microRNA miR-198 acts as a tumor suppressor across multiple cancer types and is involved in the regulation of various oncogenic factors involved in migration, proliferation, induction of apoptosis, and drug resistance [ 34 , 35 ]. Overexpression or exogenous delivery of miR-198 leads to profound phenotypic effects including decreased cell proliferation, migration, and invasion in vitro and reduced tumor progression in xenograft tumors in vivo [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

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Nanoparticle-Mediated Therapy with miR-198 Sensitizes Pancreatic Cancer to Gemcitabine Treatment through Downregulation of VCP-Mediated Autophagy

Marin-Muller,

Li,

Lü

et al. 2023

Pharmaceutics

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Pancreatic ductal adenocarcinoma (PDAC) remains an extremely aggressive disease characterized by rapidly acquired multi-drug resistance, including to first-line chemotherapeutic agent gemcitabine. Autophagy is a process that is often exploited by cancer and is one of several intrinsic factors associated with resistance to gemcitabine. We have previously found that miR-198 acts as a tumor suppressor in PDAC through the targeting of factors including Valosin-containing protein (VCP). VCP has been reported to play an important role in autophagic flux. In this study, we investigated whether the repression of VCP through miR-198 administration disrupts the autophagy process and sensitizes PDAC cells to gemcitabine treatment in vitro. Moreover, we used LGA-PEI (LPNP) nanoparticles to effectively administer miR-198 to tumors in vivo, inducing tumor sensitization to gemcitabine and leading to a significant reduction in tumor burden and metastases and a concomitant downregulation of VCP expression and autophagy maturation. Our results indicate a potential therapeutic strategy for targeting gemcitabine resistant PDAC and establishes the use of LPNPs for effective therapeutic delivery of nucleic acids in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nanoparticle-Mediated Therapy with miR-198 Sensitizes Pancreatic Cancer to Gemcitabine Treatment through Downregulation of VCP-Mediated Autophagy

Marin-Muller,

Li,

Lü

et al. 2023

Pharmaceutics

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“…It has been shown that hsa-miR-198 is able to differentiate CP from PDAC ( Vychytilova-Faltejskova et al, 2015 ). In addition, the hsa-miR-198 can act as a tumor suppressor depending on the type of cancer ( Kaushik and KumakR, 2022 ). As a result, we speculate that hsa-miR-198 may contribute to PDAC pathophysiological development through inflammatory processes.…”

Section: Discussionmentioning

confidence: 99%

Exploring the key genetic association between chronic pancreatitis and pancreatic ductal adenocarcinoma through integrated bioinformatics

et al. 2023

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Background: Pancreatic ductal adenocarcinoma (PDAC) develops rapidly and has a poor prognosis. It has been demonstrated that pancreatic ductal adenocarcinoma and chronic pancreatitis (CP) have a close connection. However, the underlying mechanisms for chronic pancreatitis transforming into pancreatic ductal adenocarcinoma are still unclear. The purpose of this study was to identify real hub genes in the development of chronic pancreatitis and pancreatic ductal adenocarcinoma.Methods: RNA-seq data of chronic pancreatitis and pancreatic ductal adenocarcinoma were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to construct a gene co-expression network between chronic pancreatitis and pancreatic ductal adenocarcinoma. GEO2R and a Venn diagram were used to identify differentially expressed genes. Then visualized networks were constructed with ClueGO, and modules of PPI network were calculated by MCODE plugin. Further validation of the results was carried out in two additional cohorts. Analyses of CEL-coexpressed genes and regulators including miRNAs and transcription factors were performed by using the corresponding online web tool. Finally, the influence of CEL in the tumor immune microenvironment (TIME) was assessed by immune contextual analysis.Results: With the help of WGCNA and GEO2R, four co-expression modules and six hub genes were identified, respectively. ClueGO enrichment analysis and MCODE cluster analysis revealed that the dysfunctional transport of nutrients and trace elements might contribute to chronic pancreatitis and pancreatic ductal adenocarcinoma development. The real hub gene CEL was identified with a markedly low expression in pancreatic ductal adenocarcinoma in external validation sets. According to the miRNA-gene network construction, hsa-miR-198 may be the key miRNA. A strong correlation exists between CEL and TIME after an evaluation of the influence of CEL in TIME.Conclusion: Our study revealed the dysfunctional transport of nutrients and trace elements may be common pathogenesis of pancreatic ductal adenocarcinoma and chronic pancreatitis. Examination on these common pathways and real hub genes may shed light on the underlying mechanism.

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