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An Overview of Targeting Legumain for Inhibiting Cancers

[ Vol. 27 , Issue. 31 ]

Author(s):

Bandi Deepa Reddy, Narasimha M Beeraka, CH. M. Kumari Chitturi and SubbaRao V. Madhunapantula*   Pages 3337 - 3348 ( 12 )

Abstract:


Legumain (LGMN; EC: 3.4.22.34), an asparaginyl endopeptidase (AEP) or asparaginyl carboxypeptidase (ACP), is a member of the C13 family of cysteine proteases. Elevated expression of LGMN is reported not only in the tumor cells of breast, prostate, and liver but also in the macrophages of the tumor microenvironment. Hence, LGMN is considered as a key protein involved in the regulation of tumor angiogenesis, invasion, and metastasis. Targeting LGMN using siRNA or pharmacological agents and peptides was reported to reduce cancer cell proliferation in vitro and shrink tumor size in vivo. Moreover, expression of LGMN is significantly low in normal cells compared to tumor cells or tumor-associated macrophages (TAMs); hence, legumain can be used as a marker for tumor recognition and targeting. Therefore, approaches inhibiting LGMN expression or activity are more viable, less toxic, and help in developing the targeted therapeutics. However, to date, LGMN targeting strategies have not been well reported. In this review, an attempt was made to summarize articles pertaining to LGMN (a) structure and activity; (b) oncogenic nature; (c) pharmacological inhibitors; and (d) targeting approaches that inhibit tumor growth. Furthermore, a list of existing gaps in LGMN research is highlighted, which needs additional studies.

Keywords:

Legumain, cancers, TAMs, metastasis, targeted therapies, DNA vaccines, miRNAs.

Affiliation:

Department of Applied Microbiology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupati, Andhra Pradesh- 517502, Center of Excellence in Molecular Biology and Regenerative Medicine, Department of Biochemistry, (A DST-FIST Sponsored Department), JSS Medical College, JSS Academy of Higher Education & Research, Mysore - 570 015, Karnataka, Department of Applied Microbiology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupati, Andhra Pradesh- 517502, Center of Excellence in Molecular Biology and Regenerative Medicine, Department of Biochemistry, (A DST-FIST Sponsored Department), JSS Medical College, JSS Academy of Higher Education & Research, Mysore - 570 015, Karnataka



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