PMID- 37531267 OWN - NLM STAT- MEDLINE DCOM- 20230907 LR - 20231225 IS - 1573-4935 (Electronic) IS - 0144-8463 (Print) IS - 0144-8463 (Linking) VI - 43 IP - 9 DP - 2023 Sep 27 TI - Involvement of DPP3 in modulating oncological features and oxidative stress response in esophageal squamous cell carcinoma. LID - 10.1042/BSR20222472 [doi] LID - BSR20222472 AB - Resistance to therapy in esophageal squamous cell carcinoma (ESCC) is a critical clinical problem and identification of novel therapeutic targets is highly warranted. Dipeptidyl peptidase III (DPP3) is a zinc-dependent aminopeptidase and functions in the terminal stages of the protein turnover. Several studies have reported overexpression and oncogenic functions of DPP3 in numerous malignancies. The present study aimed to determine the expression pattern and functional role of DPP3 in ESCC. DPP3 expression was assessed in normal and tumor tissues using quantitative real-time (qRT)-PCR and corroborated with ESCC gene expression datasets from Gene Expression Omnibus (GEO) and The cancer genome atlas (TCGA). DPP3 stable knockdown was performed in ESCC cells by shRNA and its effect on cell proliferation, migration, cell cycle, apoptosis, and activation of nuclear factor erythroid 2-related factor 2 (NRF2) pathway was assessed. The results suggested that DPP3 is overexpressed in ESCC and its knockdown leads to reduced proliferation, increased apoptosis, and inhibited migration of ESCC cells. Additionally, DPP3 knockdown leads to down-regulation of the NRF2 pathway proteins, such as NRF2, G6PD, and NQO1 along with increased sensitivity toward oxidative stress-induced cell death and chemotherapy. Conclusively, these results demonstrate critical role of DPP3 in ESCC and DPP3/NRF2 axis may serve as an attractive therapeutic target against chemoresistance in this malignancy. CI - (c) 2023 The Author(s). FAU - Arora, Mohit AU - Arora M AUID- ORCID: 0000-0002-7417-5036 AD - Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India. FAU - Kumari, Sarita AU - Kumari S AUID- ORCID: 0000-0002-9566-2933 AD - Laboratory Oncology Unit, Dr. BRA-IRCH, All India Institute of Medical Sciences, New Delhi, India. FAU - Kadian, Lokesh AU - Kadian L AD - Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India. FAU - Anupa, Geethadevi AU - Anupa G AD - Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India. FAU - Singh, Jay AU - Singh J AD - Laboratory Oncology Unit, Dr. BRA-IRCH, All India Institute of Medical Sciences, New Delhi, India. FAU - Kumar, Anurag AU - Kumar A AUID- ORCID: 0000-0002-5283-1821 AD - Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India. FAU - Verma, Deepika AU - Verma D AD - Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India. FAU - Pramanik, Raja AU - Pramanik R AD - Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India. FAU - Kumar, Sunil AU - Kumar S AD - Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India. FAU - Yadav, Rajni AU - Yadav R AD - Department of Pathology, All India Institute of Medical Sciences, New Delhi, India. FAU - Chopra, Anita AU - Chopra A AUID- ORCID: 0000-0002-0238-8702 AD - Laboratory Oncology Unit, Dr. BRA-IRCH, All India Institute of Medical Sciences, New Delhi, India. FAU - Chauhan, Shyam S AU - Chauhan SS AUID- ORCID: 0000-0002-4796-5171 AD - Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India. LA - eng GR - IA/CPHI/17/1/503333/WTDBT_/DBT-Wellcome Trust India Alliance/India PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Biosci Rep JT - Bioscience reports JID - 8102797 RN - 0 (NF-E2-Related Factor 2) RN - EC 3.4.14.4 (DPP3 protein, human) RN - EC 3.4.14.- (Dipeptidyl-Peptidases and Tripeptidyl-Peptidases) SB - IM MH - Humans MH - *Esophageal Squamous Cell Carcinoma/pathology MH - *Esophageal Neoplasms/pathology MH - NF-E2-Related Factor 2/metabolism MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Oxidative Stress MH - Cell Movement/genetics MH - Gene Expression Regulation, Neoplastic MH - Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/genetics PMC - PMC10500228 OTO - NOTNLM OT - Dipeptidyl peptidase OT - Nrf2 OT - esophageal cancer OT - esophageal squamous cell carcinoma OT - oxidative stress COIS- The authors declare that there are no competing interests associated with the manuscript. The present study was approved by Institute Ethics Committee and Institutional Biosafety Committee, All India Institute of Medical Sciences, New Delhi, India. EDAT- 2023/08/02 19:15 MHDA- 2023/09/07 06:42 PMCR- 2023/09/06 CRDT- 2023/08/02 12:52 PHST- 2022/12/07 00:00 [received] PHST- 2023/07/13 00:00 [revised] PHST- 2023/08/02 00:00 [accepted] PHST- 2023/09/07 06:42 [medline] PHST- 2023/08/02 19:15 [pubmed] PHST- 2023/08/02 12:52 [entrez] PHST- 2023/09/06 00:00 [pmc-release] AID - 233346 [pii] AID - BSR20222472 [pii] AID - 10.1042/BSR20222472 [doi] PST - ppublish SO - Biosci Rep. 2023 Sep 27;43(9):BSR20222472. doi: 10.1042/BSR20222472.