PMID- 36982347
OWN - NLM
STAT- MEDLINE
DCOM- 20230330
LR  - 20230331
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 6
DP  - 2023 Mar 9
TI  - Cathepsin H Knockdown Reverses Radioresistance of Hepatocellular Carcinoma via 
      Metabolic Switch Followed by Apoptosis.
LID - 10.3390/ijms24065257 [doi]
LID - 5257
AB  - Despite the wide application of radiotherapy in HCC, radiotherapy efficacy is 
      sometimes limited due to radioresistance. Although radioresistance is reported 
      with high glycolysis, the underlying mechanism between radioresistance and cancer 
      metabolism, as well as the role of cathepsin H (CTSH) within it, remain unclear. 
      In this study, tumor-bearing models and HCC cell lines were used to observe the 
      effect of CTSH on radioresistance. Proteome mass spectrometry, followed by 
      enrichment analysis, were used to investigate the cascades and targets regulated 
      by CTSH. Technologies such as immunofluorescence co-localization flow cytometry 
      and Western blot were used for further detection and verification. Through these 
      methods, we originally found CTSH knockdown (KD) perturbed aerobic glycolysis and 
      enhanced aerobic respiration, and thus promoted apoptosis through up-regulation 
      and the release of proapoptotic factors such as AIFM1, HTRA2, and DIABLO, 
      consequently reducing radioresistance. We also found that CTSH, together with its 
      regulatory targets (such as PFKL, HK2, LDH, and AIFM1), was correlated with 
      tumorigenesis and poor prognosis. In summary, our study found that the cancer 
      metabolic switch and apoptosis were regulated by CTSH signaling, leading to the 
      occurrence of radioresistance in HCC cells and suggesting the potential value of 
      HCC diagnosis and therapy.
FAU - Chen, Qiao
AU  - Chen Q
AD  - Department of Radiation Medicine, School of Public Health, Jilin University, 
      Changchun 130021, China.
AD  - Department of Radiation Medicine, School of Public Health and Management, Wenzhou 
      Medical University, Wenzhou 325035, China.
FAU - Qu, Shugen
AU  - Qu S
AD  - Department of Radiation Medicine, School of Public Health and Management, Wenzhou 
      Medical University, Wenzhou 325035, China.
FAU - Liang, Zhenzhen
AU  - Liang Z
AD  - Department of Radiation Medicine, School of Public Health and Management, Wenzhou 
      Medical University, Wenzhou 325035, China.
FAU - Liu, Yi
AU  - Liu Y
AD  - Department of Radiation Medicine, School of Public Health and Management, Wenzhou 
      Medical University, Wenzhou 325035, China.
FAU - Chen, Huajian
AU  - Chen H
AD  - Department of Radiation Medicine, School of Public Health and Management, Wenzhou 
      Medical University, Wenzhou 325035, China.
FAU - Ma, Shumei
AU  - Ma S
AD  - Department of Radiation Medicine, School of Public Health and Management, Wenzhou 
      Medical University, Wenzhou 325035, China.
FAU - Liu, Xiaodong
AU  - Liu X
AD  - Department of Radiation Medicine, School of Public Health, Jilin University, 
      Changchun 130021, China.
AD  - Department of Radiation Medicine, School of Public Health and Management, Wenzhou 
      Medical University, Wenzhou 325035, China.
LA  - eng
GR  - 81773363/National Natural Science Foundation of China/
GR  - 81972969/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20230309
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - EC 3.4.22.16 (Cathepsin H)
SB  - IM
MH  - Humans
MH  - *Carcinoma, Hepatocellular/genetics/radiotherapy/metabolism
MH  - *Liver Neoplasms/genetics/radiotherapy/metabolism
MH  - Cathepsin H/metabolism
MH  - Signal Transduction
MH  - Apoptosis/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Glycolysis
MH  - Cell Proliferation
MH  - Cell Line, Tumor
PMC - PMC10049059
OTO - NOTNLM
OT  - aerobic respiration
OT  - apoptosis
OT  - glycolysis
OT  - hepatocellular carcinoma
OT  - radioresistance
OT  - radiotherapy
COIS- The authors declare no conflict of interest.
EDAT- 2023/03/30 06:00
MHDA- 2023/03/30 06:11
PMCR- 2023/03/09
CRDT- 2023/03/29 01:36
PHST- 2023/02/17 00:00 [received]
PHST- 2023/03/01 00:00 [accepted]
PHST- 2023/03/30 06:11 [medline]
PHST- 2023/03/29 01:36 [entrez]
PHST- 2023/03/30 06:00 [pubmed]
PHST- 2023/03/09 00:00 [pmc-release]
AID - ijms24065257 [pii]
AID - ijms-24-05257 [pii]
AID - 10.3390/ijms24065257 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Mar 9;24(6):5257. doi: 10.3390/ijms24065257.