PMID- 35847878
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231105
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 12
DP  - 2022
TI  - RAC3 Inhibition Induces Autophagy to Impair Metastasis in Bladder Cancer Cells 
      via the PI3K/AKT/mTOR Pathway.
PG  - 915240
LID - 10.3389/fonc.2022.915240 [doi]
LID - 915240
AB  - BACKGROUND: Bladder cancer (BCa) is one of the most frequent malignant tumors 
      globally, with a significant morbidity and mortality rate. Gene expression 
      dysregulation has been proven to play a critical role in tumorigenesis. 
      Ras-related C3 botulinum toxin substrate3 (RAC3), which is overexpressed in 
      several malignancies and promotes tumor progression, has been identified as an 
      oncogene. However, RAC3 has important but not fully understood biological 
      functions in cancer. Our research aims to reveal the new functions and potential 
      mechanisms of RAC3 involved in BCa progression. METHODS: We explored the 
      expression level of RAC3 and its relationship with prognosis by publicly 
      accessible BCa datasets, while the correlation of RAC3 expression with 
      clinicopathological variables of patients was analyzed. In vitro and in vivo 
      proliferation, migration, autophagy, and other phenotypic changes were examined 
      by constructing knockdown(KD)/overexpression(OE) RAC3 cells and their association 
      with PI3K/AKT/mTOR pathway was explored by adding autophagy-related compounds. 
      RESULTS: Compared with non-tumor samples, RAC3 was highly expressed in BCa and 
      negatively correlated with prognosis. KD/OE RAC3 inhibited/promoted the 
      proliferation and migration of BCa cells. Knockdown RAC3 caused cell cycle arrest 
      and decreased adhesion without affecting apoptosis. Inhibition of RAC3 activates 
      PI3K/AKT/mTOR mediated autophagy and inhibits proliferation and migration of BCa 
      cells in vivo and in vitro. Autophagy inhibitor 3MA can partially rescue the 
      metastasis and proliferation inhibition effect caused by RAC3 inhibition. 
      Inhibit/activate mTOR enhanced/impaired autophagy, resulting in shRAC3-mediated 
      migration defect exacerbated/rescued. CONCLUSION: RAC3 is highly expressed in 
      BCa. It is associated with advanced clinicopathological variables and poor 
      prognosis. Knockdown RAC3 exerts an antitumor effect by enhancing PI3K/AKT/mTOR 
      mediated autophagy. Targeting RAC3 and autophagy simultaneously is a potential 
      therapeutic strategy for inhibiting BCa progression and prolonging survival.
CI  - Copyright (c) 2022 Wang, Shi, Liu, Huang, Ding, Zhao, Liu, Wang, Yang and Chen.
FAU - Wang, Liwei
AU  - Wang L
AD  - Urology Institute of People's Liberation Army, Southwest Hospital, Third Military 
      Medical University (Army Medical University), Chongqing, China.
AD  - Unit 32357 of People's Liberation Army, Pujiang, China.
FAU - Shi, Jiazhong
AU  - Shi J
AD  - Department of Cell Biology, Third Military Medical University (Army Medical 
      University), Chongqing, China.
FAU - Liu, Sha
AU  - Liu S
AD  - Department of Cell Biology, Third Military Medical University (Army Medical 
      University), Chongqing, China.
FAU - Huang, Yaqin
AU  - Huang Y
AD  - Department of Cell Biology, Third Military Medical University (Army Medical 
      University), Chongqing, China.
FAU - Ding, Hua
AU  - Ding H
AD  - Urology Institute of People's Liberation Army, Southwest Hospital, Third Military 
      Medical University (Army Medical University), Chongqing, China.
FAU - Zhao, Baixiong
AU  - Zhao B
AD  - Urology Institute of People's Liberation Army, Southwest Hospital, Third Military 
      Medical University (Army Medical University), Chongqing, China.
FAU - Liu, Yuting
AU  - Liu Y
AD  - Urology Institute of People's Liberation Army, Southwest Hospital, Third Military 
      Medical University (Army Medical University), Chongqing, China.
FAU - Wang, Wuxing
AU  - Wang W
AD  - Urology Institute of People's Liberation Army, Southwest Hospital, Third Military 
      Medical University (Army Medical University), Chongqing, China.
FAU - Yang, Jin
AU  - Yang J
AD  - Department of Cell Biology, Third Military Medical University (Army Medical 
      University), Chongqing, China.
FAU - Chen, Zhiwen
AU  - Chen Z
AD  - Urology Institute of People's Liberation Army, Southwest Hospital, Third Military 
      Medical University (Army Medical University), Chongqing, China.
LA  - eng
PT  - Journal Article
DEP - 20220630
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC9279623
OTO - NOTNLM
OT  - PI3K/AKT/mTOR
OT  - RAC3
OT  - autophagy
OT  - bladder cancer
OT  - metastasis
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- 2022/07/19 06:00
MHDA- 2022/07/19 06:01
PMCR- 2022/01/01
CRDT- 2022/07/18 04:22
PHST- 2022/04/07 00:00 [received]
PHST- 2022/05/30 00:00 [accepted]
PHST- 2022/07/18 04:22 [entrez]
PHST- 2022/07/19 06:00 [pubmed]
PHST- 2022/07/19 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2022.915240 [doi]
PST - epublish
SO  - Front Oncol. 2022 Jun 30;12:915240. doi: 10.3389/fonc.2022.915240. eCollection 
      2022.