PMID- 37203409
OWN - NLM
STAT- MEDLINE
DCOM- 20230525
LR  - 20230525
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Linking)
VI  - 52
IP  - 1
DP  - 2023 Jul
TI  - HINT3 suppresses AKT/mTOR signaling pathway activity during breast cancer 
      tumorigenesis through PTEN transcriptional activation.
LID - 54 [pii]
LID - 10.3892/ijmm.2023.5257 [doi]
AB  - Histidine triad nucleotide‑binding protein (HINT) belongs to the histidine triad 
      protein family. Recent studies have demonstrated that HINT1 and HINT2 both play a 
      pivotal role in cancer growth. However, the functions of HINT3 in various types 
      of cancer, including breast cancer (BRCA), have not yet been fully elucidated. In 
      the present study, the role of HINT3 in BRCA was investigated. Based on The 
      Cancer Genome Atlas and reverse transcription‑quantitative PCR analyses, HINT3 
      was found to be decreased in BRCA tissues. In vitro, HINT3 knockdown promoted the 
      proliferation and colony formation of, and 5‑ethynyl‑2'‑deoxyuridine 
      incorporation in MCF‑7 and MDA‑MB‑231 BRCA cells. By contrast, HINT3 
      overexpression suppressed DNA synthesis and the proliferation of both cell lines. 
      Apoptosis was also found to be modulated by HINT3. In vivo, HINT3 ectopic 
      expression attenuated the tumorigenesis of MDA‑MB‑231 and MCF‑7 cells in a mouse 
      tumor xenograft model. Furthermore, HINT3 silencing or overexpression also 
      enhanced or inhibited, respectively, the migratory capacity of the MCF‑7 and 
      MDA‑MB‑231 cells. Finally, HINT3 upregulated phosphatase and tensin homolog 
      (PTEN) at the transcriptional level, which resulted in the inactivation of 
      AKT/mammalian target of rapamycin (mTOR) signaling both in vitro and in vivo. 
      Taken together, the present study demonstrates that HINT3 inhibits the activation 
      of the PTEN/AKT/mTOR signaling pathway, and suppresses the proliferation, growth, 
      migration and tumor development of MCF‑7 and MDA‑MB‑231 BRCA cells.
FAU - Li, Jinping
AU  - Li J
AD  - Department of Surgical Oncology, General Hospital of Ningxia Medical University, 
      Yinchuan, Ningxia 750004, P.R. China.
FAU - Liu, Yaobang
AU  - Liu Y
AD  - Department of Surgical Oncology, General Hospital of Ningxia Medical University, 
      Yinchuan, Ningxia 750004, P.R. China.
FAU - Lian, Bing
AU  - Lian B
AD  - Department of Surgical Oncology, General Hospital of Ningxia Medical University, 
      Yinchuan, Ningxia 750004, P.R. China.
FAU - Li, Hong
AU  - Li H
AD  - Department of Surgical Oncology, General Hospital of Ningxia Medical University, 
      Yinchuan, Ningxia 750004, P.R. China.
FAU - Chai, Dahai
AU  - Chai D
AD  - Department of Surgical Oncology, General Hospital of Ningxia Medical University, 
      Yinchuan, Ningxia 750004, P.R. China.
FAU - Gao, Yali
AU  - Gao Y
AD  - Department of Surgical Oncology, General Hospital of Ningxia Medical University, 
      Yinchuan, Ningxia 750004, P.R. China.
FAU - Wang, Yanbai
AU  - Wang Y
AD  - Department of Surgical Oncology, General Hospital of Ningxia Medical University, 
      Yinchuan, Ningxia 750004, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20230519
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (HINT1 protein, human)
RN  - 0 (Hint2 protein, human)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - 0 (Nerve Tissue Proteins)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Female
MH  - Humans
MH  - Mice
MH  - *Breast Neoplasms/genetics/metabolism
MH  - Carcinogenesis/genetics
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - Cell Transformation, Neoplastic
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - *Proto-Oncogene Proteins c-akt/metabolism
MH  - PTEN Phosphohydrolase/genetics/metabolism
MH  - Signal Transduction/genetics
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
MH  - Transcriptional Activation
OTO - NOTNLM
OT  - breast cancer
OT  - histidine triad nucleotide‑binding protein 3
OT  - migration
OT  - phosphatase and tensin homolog/AKT
OT  - proliferation
EDAT- 2023/05/19 06:42
MHDA- 2023/05/22 06:42
CRDT- 2023/05/19 04:23
PHST- 2021/11/12 00:00 [received]
PHST- 2023/02/02 00:00 [accepted]
PHST- 2023/05/22 06:42 [medline]
PHST- 2023/05/19 06:42 [pubmed]
PHST- 2023/05/19 04:23 [entrez]
AID - 54 [pii]
AID - 10.3892/ijmm.2023.5257 [doi]
PST - ppublish
SO  - Int J Mol Med. 2023 Jul;52(1):54. doi: 10.3892/ijmm.2023.5257. Epub 2023 May 19.