PMID- 30046387
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 53
DP  - 2018 Jul 10
TI  - miR-363 confers taxane resistance in ovarian cancer by targeting the Hippo 
      pathway member, LATS2.
PG  - 30053-30065
LID - 10.18632/oncotarget.25698 [doi]
AB  - Ovarian cancer is the most aggressive female reproductive tract tumours. Taxane 
      (paclitaxel; TX) is widely used for ovarian cancer treatment. However, ovarian 
      cancers often acquire chemoresistance. MicroRNAs (miR) have been reported to 
      mediate many tumours'chemoresistance. We investigated the role of miR-363 in the 
      chemoresistance of the ovarian cancer cell line, KF, and its TX-resistant 
      derivative (KF-TX) cells. QRT-PCR indicated that miR-363 was upregulated in KF-TX 
      cells, and introduction of miR-363 into sensitive ovarian cancer cells confers 
      TX-resistance and significantly inhibited the expression of the Hippo member, 
      LATS2, as indicated by viability, clonogenic assay and expression analysis. 
      Furthermore, we validated the role of LATS2 in TX-response by sh-based silencing, 
      which also confers TX-resistance to the ovarian cancer cells. On the other hand, 
      specific inhibitor against miR-363 restored the response to TX in the resistant 
      cells. In addition, miR-363 was found to bind to the 3'-UTR of LATS2 mRNA, 
      confirming that miR-363 directly targets LATS2 as indicated by dual luciferase 
      assay. RT-PCR-based evaluation of miR-363 in a panel of human ovarian tumours 
      revealed its upregulation in most of the tumour tissues identified as resistant 
      while it was downregulated in most of the tissues identified as sensitive ones. 
      Moreover, higher levels of miR-363 in human ovarian cancer specimens were 
      significantly correlated with TX chemoresistance. Taken together, our study 
      reveals the involvement of miR-363 in chemoresistance by targeting LATS2 in 
      ovarian cancers, raising the possibility that combination therapy with a miR-363 
      inhibitor and TX may increase TX efficacy and reduce the chance of TX-resistance.
FAU - Mohamed, Zeinab
AU  - Mohamed Z
AD  - Zoology Department, Faculty of Science, Aswan University, Aswan, Egypt.
AD  - Department of Obstetrics and Gynaecology, Hokkaido University Graduate School of 
      Medicine, Sapporo, Japan.
FAU - Hassan, Mohamed Kamel
AU  - Hassan MK
AD  - Department of Obstetrics and Gynaecology, Hokkaido University Graduate School of 
      Medicine, Sapporo, Japan.
AD  - Bitechnology Program, Zoology Department, Faculty of Science, Port Said 
      University, Port Said, Egypt.
AD  - Centre for Genomics, HelmyInstitute for Medical Sciences, Zewail City for Science 
      and Technology, Giza, Egypt.
FAU - Okasha, Safwat
AU  - Okasha S
AD  - Zoology Department, Faculty of Science, Aswan University, Aswan, Egypt.
FAU - Mitamura, Takashi
AU  - Mitamura T
AD  - Department of Obstetrics and Gynaecology, Hokkaido University Graduate School of 
      Medicine, Sapporo, Japan.
FAU - Keshk, Sarah
AU  - Keshk S
AD  - Bitechnology Program, Zoology Department, Faculty of Science, Port Said 
      University, Port Said, Egypt.
AD  - Centre for Genomics, HelmyInstitute for Medical Sciences, Zewail City for Science 
      and Technology, Giza, Egypt.
FAU - Konno, Yusuke
AU  - Konno Y
AD  - Department of Obstetrics and Gynaecology, Hokkaido University Graduate School of 
      Medicine, Sapporo, Japan.
FAU - Kato, Tatsuya
AU  - Kato T
AD  - Department of Obstetrics and Gynaecology, Hokkaido University Graduate School of 
      Medicine, Sapporo, Japan.
FAU - El-Khamisy, Sherif F
AU  - El-Khamisy SF
AD  - Centre for Genomics, HelmyInstitute for Medical Sciences, Zewail City for Science 
      and Technology, Giza, Egypt.
AD  - Krebs and Sheffield Institute for Nucleic Acids, University of Sheffield, 
      Sheffield, UK.
FAU - Ohba, Yusuke
AU  - Ohba Y
AD  - Department of Cell Physiology, Hokkaido University Graduate School of Medicine, 
      Sapporo, Japan.
FAU - Watari, Hidemichi
AU  - Watari H
AD  - Department of Obstetrics and Gynaecology, Hokkaido University Graduate School of 
      Medicine, Sapporo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20180710
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC6059020
OTO - NOTNLM
OT  - LATS2
OT  - chemoresistance
OT  - miR-363
OT  - ovarian cancer
OT  - taxane
COIS- CONFLICTS OF INTEREST The authors declare there is no conflicts of interest
EDAT- 2018/07/27 06:00
MHDA- 2018/07/27 06:01
PMCR- 2018/07/10
CRDT- 2018/07/27 06:00
PHST- 2017/11/21 00:00 [received]
PHST- 2018/06/04 00:00 [accepted]
PHST- 2018/07/27 06:00 [entrez]
PHST- 2018/07/27 06:00 [pubmed]
PHST- 2018/07/27 06:01 [medline]
PHST- 2018/07/10 00:00 [pmc-release]
AID - 25698 [pii]
AID - 10.18632/oncotarget.25698 [doi]
PST - epublish
SO  - Oncotarget. 2018 Jul 10;9(53):30053-30065. doi: 10.18632/oncotarget.25698. 
      eCollection 2018 Jul 10.