MicroRNA in Pancreatic Cancer: From Biology to Therapeutic Potential

Rawat, Manmeet; Kadian, Kavita; Gupta, Yash; Kumar, Anand; Chain, Patrick; Kovbasnjuk, Olga; Kumar, Suneel; Parasher, Gulshan

doi:10.3390/genes10100752

Cited by 85 publications

(65 citation statements)

References 162 publications

(199 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Over the last decade, by applying the latest genomics analysis methods, the search for miRNAs whose expressions are altered in PDAC cells has been energetically carried out [ 15 , 16 , 17 ]. A vast number of studies in PDAC cells have revealed that dysregulated miRNAs are deeply involved in the malignant transformation of cancer cells, e.g., cell cycle runaway, suppression of apoptosis, promotion of cell invasion and metastasis, and acquisition of drug resistance [ 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of miR-30c-5p and miR-30c-2-3p Regulation on Oncogenic Genes

Tanaka

Okada

Hozaka

et al. 2020

Cancers

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive types of cancer, and its prognosis is abysmal; only 25% of patients survive one year, and 5% live for five years. MicroRNA (miRNA) signature analysis of PDAC revealed that both strands of pre-miR-30c (miR-30c-5p, guide strand; miR-30c-2-3p, passenger strand) were significantly downregulated, suggesting they function as tumor-suppressors in PDAC cells. Ectopic expression assays demonstrated that these miRNAs attenuated the aggressiveness of PDAC cells, e.g., cell proliferation, migration, and invasiveness. Through a combination of in silico analyses and gene expression data, we identified 216 genes as putative oncogenic targets of miR-30c-5p and miR-30c-2-3p regulation in PDAC cells. Among these, the expression of 18 genes significantly predicted the 5-year survival rates of PDAC patients (p < 0.01). Importantly, the expression levels of 10 genes (YWHAZ, F3, TMOD3, NFE2L3, ENDOD1, ITGA3, RRAS, PRSS23, TOP2A, and LRRFIP1) were found to be independent prognostic factors for patient survival (p < 0.01). We focused on TOP2A (DNA Topoisomerase II Alpha) and investigated its potential as a therapeutic target for PDAC. The overexpression of TOP2A and its transcriptional activators (SP1 and HMGB2) was detected in PDAC clinical specimens. Moreover, the knockdown of TOP2A enhanced the sensitivity of PDAC cells to anticancer drugs. Our analyses of the PDAC miRNA signature and tumor-suppressive miRNAs provide important insights into the molecular pathogenesis of PDAC.

show abstract

Section: Introductionmentioning

confidence: 99%

Molecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of miR-30c-5p and miR-30c-2-3p Regulation on Oncogenic Genes

Tanaka

Okada

Hozaka

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…In the last decade, genomics analysis methods have been actively used to identify miRNAs aberrantly expressed in various cancer cells [20,21]. Our miRNA expression profile generated by RNA sequencing provided us with new information about dysregulated miRNAs in PDAC cells [22][23][24]. Our miRNA signatures have revealed that some passenger strands of miRNAs were significantly downregulated in cancerous tissues, including miR-30a-3p and miR-30c-2-3p [25][26][27].…”

Section: Discussionmentioning

confidence: 99%

Role of miR-30a-3p Regulation of Oncogenic Targets in Pancreatic Ductal Adenocarcinoma Pathogenesis

Shimomura

Okada

Tanaka

et al. 2020

IJMS

View full text Add to dashboard Cite

Our recent studies have implicated some passenger strands of miRNAs in the molecular pathogenesis of human cancers. Analysis of the microRNA (miRNA) expression signature in pancreatic ductal adenocarcinoma (PDAC) has shown that levels of miR-30a-3p, the passenger strand derived from pre-mir-30a, are significantly downregulated in PDAC tissues. This study aimed to identify the oncogenes closely involved in PDAC molecular pathogenesis under the regulation of miR-30a-3p. Ectopic expression assays showed that miR-30a-3p expression inhibited the aggressiveness of the PDAC cells, suggesting that miR-30a-3p acts as a tumor-suppressive miRNA in PDAC cells. We further identified 102 putative targets of miR-30a-3p regulation in PDAC cells by combining in silico analysis with gene expression data. Of these, ten genes (EPS8, HMGA2, ENDOD1, SLC39A10, TGM2, MGLL, SERPINE1, ITGA2, DTL, and UACA) were independent prognostic factors in multivariate analysis of survival of patients with PDAC (p < 0.01). We also investigated the oncogenic function of the integrin ITGA2 in PDAC cell lines. The integrin family comprises cell adhesion molecules expressed as heterodimeric, transmembrane proteins on the surface of various cells. Overexpression of ITGA2/ITGB1 (an ITGA2 binding partner) was detected in the PDAC clinical specimens. The knockdown of ITGA2 expression attenuated the malignant phenotypes of the PDAC cells. Together, results from these microRNA-based approaches can accelerate our understanding of PDAC molecular pathogenesis.

show abstract

“…In pancreatic cancer, several studies have demonstrated its role in diagnosis, prognosis, and as a potential therapeutic target. 17 Besides, due to its relative stability of miRNAs and easy extraction of miRNAs in body fluids such as plasma, it has become a novel biomarker for non-invasive detection of cancer. 18 Although there are few studies on miR-934 in the field of tumors, it has been proved to play a role in the development of various tumors.…”

Section: Discussionmentioning

confidence: 99%

<p>miR-934 as a Prognostic Marker Facilitates Cell Proliferation and Migration of Pancreatic Tumor by Targeting PROX1</p>

Jin

Weng

Wang

et al. 2020

OTT

View full text Add to dashboard Cite

Background: Pancreatic cancer is an extremely lethal digestive cancer with late diagnosis and poor prognosis. miR-934 has been reported to serve as an oncogene in multiple cancers, such as ovarian cancer and bladder cancer. However, its role in pancreatic cancer remains undiscovered. Materials and Methods: The expression data of miR-934 were obtained from the Gene Expression Omnibus database and from our own patient samples. The clinicopathological data and corresponding follow-up data were retrieved from The Cancer Genome Atlas database. CCK8 and colony formation assays were conducted to measure cell proliferation capacity in vitro. Wound healing and transwell assays were performed to detect the migration ability of pancreatic cancer cell. Results: We found that miR-934 was significantly upregulated in pancreatic tumor samples and cell lines. The expression of miR-934 was related to pathological stages. Upregulated miR-934 was associated with poor prognosis in patients with pancreatic cancer. Mir-934 inhibition reduced, while overexpression promoted, cell proliferation and migration. Mechanically, we found miR-934 could directly bind to 3ʹ-UTR of PROX1 leading to mRNA derogation. Furthermore, increased cell proliferation and migration caused by miR-934 overexpression could be reversed by forced PROX1 expression. Conclusion: miR-934 is an oncogene in pancreatic cancer and could serve as a prognosis indicator for patients with pancreatic cancer, suggesting that miR-934 is a promising therapeutic target for pancreatic cancer.

show abstract

MicroRNA in Pancreatic Cancer: From Biology to Therapeutic Potential

Cited by 85 publications

References 162 publications

Molecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of miR-30c-5p and miR-30c-2-3p Regulation on Oncogenic Genes

Molecular Pathogenesis of Pancreatic Ductal Adenocarcinoma: Impact of miR-30c-5p and miR-30c-2-3p Regulation on Oncogenic Genes

Role of miR-30a-3p Regulation of Oncogenic Targets in Pancreatic Ductal Adenocarcinoma Pathogenesis

<p>miR-934 as a Prognostic Marker Facilitates Cell Proliferation and Migration of Pancreatic Tumor by Targeting PROX1</p>

Contact Info

Product

Resources

About