Shedding more light on the role of Midkine in hepatocellular carcinoma: New perspectives on diagnosis and therapy

• Published in: IUBMB life 2021-04, Vol.73 (4), p.659-669
• Main Authors: Gowhari Shabgah, Arezoo, Ezzatifar, Fatemeh, Aravindhan, Surendar, Olegovna Zekiy, Angelina, Ahmadi, Majid, Gheibihayat, Seyed Mohammad, Gholizadeh Navashenaq, Jamshid
• Format: Article
• Language: English
• Subjects: Abbreviations; AFP Alpha‐feto preotein; ALK Anaplastic lymphoma kinase; Angiogenesis; Animals; Anoikis; Apoptosis; biomarker; Biomarkers, Tumor - blood; cancer; Carcinoma, Hepatocellular - diagnosis; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - therapy; Cell migration; Cell viability; Diagnosis; DRDeath receptor; ECMExtracellular matrix; EMT Epithelial‐mesenchymal transition; ERKExtracellular‐signal‐regulated kinase; gene therapy; Genetic Therapy - methods; HCCHepatocellular Carcinoma; Hepatocellular carcinoma; Humans; IGF‐1RInsulin‐like growth factor‐1 receptor; Immunotherapy - methods; Inflammation; IRS‐1Insulin receptor substrate‐1; JAKJanus kinase; JNK c‐Jun N‐terminal kinases; Liver - blood supply; Liver - pathology; Liver cancer; Liver Neoplasms - diagnosis; Liver Neoplasms - pathology; Liver Neoplasms - therapy; LRP‐1Low‐density lipoprotein receptor‐related protein; LTBP3 Latent Transforming Growth Factor Beta Binding Protein 3; MAPK Mitogen‐activated protein kinase; MDKMidkine; Metastases; Midkine; Midkine - blood; Midkine - chemistry; Midkine - physiology; NEGFNeurite growth‐promoting factor; Neovascularization, Pathologic - metabolism; NF‐κB Nuclear factor κB; PI3K Phosphoinositide 3‐kinase PGRN Progranulin; PLSCR1 Phospholipid Scramblase 1; PTNPleiotrophin; PTPζProtein tyrosine phosphatase‐ζ; RNA Interference; STAT Signal transducer and activator of transcription; TGF‐β Transforming growth factor‐β; TRAIL TNF‐related apoptosis‐inducing ligand; Tumors; VLA4Very late antigen‐4; ZFAS1 ZNFX1 antisense RNA 1
• ISSN: 1521-6543; 1521-6551
• DOI: 10.1002/iub.2458

One of the most common malignant tumors is hepatocellular carcinoma (HCC). Progression of HCC mainly results from highly complex molecular and pathological pathways. Midkine (MDK) is a growth factor that impacts viability, migration, and other cell activities. Since MDK has been involved in the inflammatory responses, it has been claimed that MDK has a crucial role in HCC. MDK acts as an anti‐apoptotic factor, which mediates tumor cell viability. In addition, MDK blocks anoikis to promote metastasis. There is also evidence that MDK is involved in angiogenesis. It has been shown that the application of anti‐MDK approaches might be promising in the treatment of HCC. Besides, due to the elevated expression in HCC, MDK has been proposed as a biomarker in the prognosis and diagnosis of HCC. In this review, we will discuss the role of MDK in HCC. It is hoped that the development of new strategies concerning MDK‐based therapies will be promising in HCC management.