Targeting cathepsin L in the regulation of apoptosis in peripheral T-cell lymphoma

다국어 초록 (Multilingual Abstract)

Backgrounds Peripheral T-cell lymphoma (PTCL) is a heterogeneous lymphoproliferative neoplasms derived from post-thymic T lymphocytes and mature NK cells. Although the incidence is rare, PTCL is frequently recurrence with pore prognosis. Cathepsin L is a member of cysteine proteases strongly related to the carcinogenesis and progression of malignant tumors.


Objectives To test the expression of cathepsin L in PTCL and to clarify the possible role of cathepsin L in the pathogenesis of PTCL.


Results The public datasheets showed a significant increase of cathepsin L in PTCL than normal T-cells. This result was confirmed by the collected tumor samples, in which the pathological changes and the immunohistochemical test were consistent with PTCL diagnosis. Two PTCL cell lines, Jurkat and Hut78, with a stable knockdown of cathepsin L were successfully established. The RNAseq analysis reported a total of eight co-differentially expressed genes between cathepsin Llow Jurkat vs vector Jurkat and cathepsin Llow Hut78 vs vector Hut78 two datasheets. The apoptosis array reported abnormal expression of several pro-apoptosis proteins including Fas, Bax, sTNF-R1, IGFBP-6, etc. According to the gene function enrichment analysis, p53 signaling pathway was involved in loss of cathepsin L in PTCL cells in vitro. In addition, the levels of above differentially expressed genes/proteins were finally checked, and our data confirmed an alteration of p53, apoptosis regulation-related factors (PAK4, SESN2) and apoptosis-related factors (Fas, Bax, sTNF-R1, and IGFBP-6).


Conclusion Taken together, we demonstrated a role of cathepsin L in apoptosis by regulation of p53 signaling pathway. Our finding might provide a new possible candidate drug target for clinical treatment of PTCL in future.

다국어 초록 (Multilingual Abstract)

Backgrounds Peripheral T-cell lymphoma (PTCL) is a heterogeneous lymphoproliferative neoplasms derived from post-thymic T lymphocytes and mature NK cells. Although the incidence is rare, PTCL is frequently recurrence with pore prognosis. Cathepsin L is a member of cysteine proteases strongly related to the carcinogenesis and progression of malignant tumors.




Objectives To test the expression of cathepsin L in PTCL and to clarify the possible role of cathepsin L in the pathogenesis of PTCL.




Results The public datasheets showed a significant increase of cathepsin L in PTCL than normal T-cells. This result was confirmed by the collected tumor samples, in which the pathological changes and the immunohistochemical test were consistent with PTCL diagnosis. Two PTCL cell lines, Jurkat and Hut78, with a stable knockdown of cathepsin L were successfully established. The RNAseq analysis reported a total of eight co-differentially expressed genes between cathepsin Llow Jurkat vs vector Jurkat and cathepsin Llow Hut78 vs vector Hut78 two datasheets. The apoptosis array reported abnormal expression of several pro-apoptosis proteins including Fas, Bax, sTNF-R1, IGFBP-6, etc. According to the gene function enrichment analysis, p53 signaling pathway was involved in loss of cathepsin L in PTCL cells in vitro. In addition, the levels of above differentially expressed genes/proteins were finally checked, and our data confirmed an alteration of p53, apoptosis regulation-related factors (PAK4, SESN2) and apoptosis-related factors (Fas, Bax, sTNF-R1, and IGFBP-6).




Conclusion Taken together, we demonstrated a role of cathepsin L in apoptosis by regulation of p53 signaling pathway. Our finding might provide a new possible candidate drug target for clinical treatment of PTCL in future.

참고문헌 (Reference)

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