PMID- 34345220
OWN - NLM
STAT- MEDLINE
DCOM- 20220317
LR  - 20220317
IS  - 1449-2288 (Electronic)
IS  - 1449-2288 (Linking)
VI  - 17
IP  - 11
DP  - 2021
TI  - MicroRNA-216b targets HK2 to potentiate autophagy and apoptosis of breast cancer 
      cells via the mTOR signaling pathway.
PG  - 2970-2983
LID - 10.7150/ijbs.48933 [doi]
AB  - Patients suffering from breast cancer (BC) still have a poor response to 
      treatments, even though early detection and improved therapy have contributed to 
      a reduced mortality. Recent studies have been inspired on the association between 
      microRNAs (miRs) and therapies of BC. The current study set out to investigate 
      the role of miR-216b in BC, and further analyze the underlining mechanism. 
      Firstly, hexokinase 2 (HK2) and miR-216b were characterized in BC tissues and 
      cells by RT-qPCR and Western blot assay. In addition, the interaction between HK2 
      and miR-216b was analyzed using dual luciferase reporter assay. BC cells were 
      further transfected with a series of miR-126b mimic or inhibitor, or siRNA 
      targeting HK2, so as to analyze the regulatory mechanism of miR-216b, HK2 and 
      mammalian target of rapamycin (mTOR) signaling pathway, and to further explore 
      their regulation in BC cellular behaviors. The results demonstrated that HK2 was 
      highly expressed and miR-216b was poorly expressed in BC cells and tissues. HK2 
      was also verified as a target of miR-216b with online databases and dual 
      luciferase reporter assay. Functionally, miR-216b was found to be closely 
      associated with BC progression via inactivating mTOR signaling pathway by 
      targeting HK2. Moreover, cell viability, migration and invasion were reduced as a 
      result of miR-216b upregulation or HK2 silencing, while autophagy, cell cycle 
      arrest and apoptosis were induced. Taken together, our findings indicated that 
      miR-216 down-regulates HK2 to inactivate the mTOR signaling pathway, thus 
      inhibiting the progression of BC. Hence, this study highlighted a novel target 
      for BC treatment.
CI  - (c) The author(s).
FAU - Liu, Ting
AU  - Liu T
AD  - The Affiliated Hospital of Qingdao University, Qingdao 266000, P.R. China.
FAU - Ye, Ping
AU  - Ye P
AD  - School of Medical Instrument and Food Engineering, University of Shanghai for 
      Science and Technology, Shanghai 200093, P.R. China.
FAU - Ye, Yuanyuan
AU  - Ye Y
AD  - The Affiliated Hospital of Qingdao University, Qingdao 266000, P.R. China.
FAU - Han, Baosan
AU  - Han B
AD  - The Affiliated Hospital of Qingdao University, Qingdao 266000, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210713
PL  - Australia
TA  - Int J Biol Sci
JT  - International journal of biological sciences
JID - 101235568
RN  - 0 (MIRN216 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.1.1 (HK2 protein, human)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Autophagy/genetics
MH  - Breast Neoplasms/genetics/metabolism/*pathology
MH  - Cell Cycle
MH  - Cell Line, Tumor
MH  - Cell Survival
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Hexokinase/*genetics
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - MicroRNAs/*genetics
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC8326127
OTO - NOTNLM
OT  - Autophagy
OT  - Breast cancer
OT  - HK2
OT  - MicroRNA-216b
OT  - mTOR signaling pathway
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2021/08/05 06:00
MHDA- 2022/03/18 06:00
PMCR- 2021/01/01
CRDT- 2021/08/04 07:05
PHST- 2020/06/01 00:00 [received]
PHST- 2021/03/22 00:00 [accepted]
PHST- 2021/08/04 07:05 [entrez]
PHST- 2021/08/05 06:00 [pubmed]
PHST- 2022/03/18 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - ijbsv17p2970 [pii]
AID - 10.7150/ijbs.48933 [doi]
PST - epublish
SO  - Int J Biol Sci. 2021 Jul 13;17(11):2970-2983. doi: 10.7150/ijbs.48933. 
      eCollection 2021.