PMID- 33392094
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210709
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 10
DP  - 2020
TI  - MicroRNA-18a-5p Suppresses Tumor Growth via Targeting Matrix Metalloproteinase-3 
      in Cisplatin-Resistant Ovarian Cancer.
PG  - 602670
LID - 10.3389/fonc.2020.602670 [doi]
LID - 602670
AB  - Cumulating evidence indicates that dysregulation of microRNAs (miRNAs) plays a 
      central role in the initiation, progression, and drug resistance of cancer cells. 
      However, the specific miRNAs contributing to drug resistance in ovarian cancer 
      cells have not been fully elucidated. Aimed to identify potential miRNAs involved 
      in platinum resistance, we performed a miRNA expression profile in 
      cisplatin-sensitive and cisplatin-resistant ovarian cancer cells, and we found 
      several differentially abundant miRNAs in the pair of cell lines. Notably, 
      miR-18a-5p (miR-18a), a member of the oncogenic associated miR-17-92 cluster, was 
      decreased in cisplatin-resistant as compared with cisplatin-sensitive cells. 
      Real-time PCR analysis confirmed these findings. We then studied the biological, 
      molecular, and therapeutic consequences of increasing the miR-18a levels with 
      oligonucleotide microRNA mimics (OMM). Compared with a negative control OMM, 
      transient transfection of a miR-18a-OMM reduced cell growth, cell proliferation, 
      and cell invasion. Intraperitoneal injections of miR-18a-OMM-loaded 
      folate-conjugated liposomes significantly reduced the tumor weight and the number 
      of nodules in ovarian cancer-bearing mice when compared with a control-OMM group. 
      Survival analysis using the Kaplan-Meier plotter database showed that ovarian 
      cancer patients with high miR-18a levels live longer in comparison to patients 
      with lower miR-18a levels. Bioinformatic analyses, real-time-PCR, Western blots, 
      and luciferase reporter assays revealed that Matrix Metalloproteinase-3 (MMP-3) 
      is a direct target of miR-18a. Small-interfering RNA (siRNA)-mediated silencing 
      of MMP-3 reduced cell viability, cell growth, and the invasiveness potential of 
      cisplatin-resistant ovarian cancer cells. Our study suggests that targeting 
      miR-18a is a plausible therapeutic strategy for cisplatin-resistant ovarian 
      cancer.
CI  - Copyright (c) 2020 Quinones-Diaz, Reyes-Gonzalez, Sanchez-Guzman, Conde-Del Moral, 
      Valiyeva, Santiago-Sanchez and Vivas-Mejia.
FAU - Quinones-Diaz, Blanca I
AU  - Quinones-Diaz BI
AD  - Department of Biochemistry, University of Puerto Rico, San Juan, Puerto Rico.
FAU - Reyes-Gonzalez, Jeyshka M
AU  - Reyes-Gonzalez JM
AD  - Department of Biochemistry, University of Puerto Rico, San Juan, Puerto Rico.
FAU - Sanchez-Guzman, Victoria
AU  - Sanchez-Guzman V
AD  - Department of Interdisciplinary Sciences, University of Puerto Rico, San Juan, 
      Puerto Rico.
FAU - Conde-Del Moral, Isabel
AU  - Conde-Del Moral I
AD  - Department of Chemistry, University of Puerto Rico, San Juan, Puerto Rico.
FAU - Valiyeva, Fatma
AU  - Valiyeva F
AD  - Comprehensive Cancer Center, University of Puerto Rico, San Juan, Puerto Rico.
FAU - Santiago-Sanchez, Ginette S
AU  - Santiago-Sanchez GS
AD  - Department of Biochemistry, University of Puerto Rico, San Juan, Puerto Rico.
FAU - Vivas-Mejia, Pablo E
AU  - Vivas-Mejia PE
AD  - Department of Biochemistry, University of Puerto Rico, San Juan, Puerto Rico.
AD  - Comprehensive Cancer Center, University of Puerto Rico, San Juan, Puerto Rico.
LA  - eng
GR  - R25 GM061838/GM/NIGMS NIH HHS/United States
GR  - U54 MD007600/MD/NIMHD NIH HHS/United States
PT  - Journal Article
DEP - 20201217
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC7774672
OTO - NOTNLM
OT  - MMP-3
OT  - cisplatin resistance
OT  - folate-liposomes
OT  - miR-18a
OT  - ovarian cancer
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/01/05 06:00
MHDA- 2021/01/05 06:01
PMCR- 2020/01/01
CRDT- 2021/01/04 05:30
PHST- 2020/09/04 00:00 [received]
PHST- 2020/11/17 00:00 [accepted]
PHST- 2021/01/04 05:30 [entrez]
PHST- 2021/01/05 06:00 [pubmed]
PHST- 2021/01/05 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2020.602670 [doi]
PST - epublish
SO  - Front Oncol. 2020 Dec 17;10:602670. doi: 10.3389/fonc.2020.602670. eCollection 
      2020.