Biological functions and therapeutic potential of SRY related high mobility group box 5 in human cancer

Abstract

Cancer is a heavy human burden worldwide, with high morbidity and mortality. Identification of novel cancer diagnostic and prognostic biomarkers is important for developing cancer treatment strategies and reducing mortality. Transcription factors, including SRY associated high mobility group box (SOX) proteins, are thought to be involved in the regulation of specific biological processes. There is growing evidence that SOX transcription factors play an important role in cancer progression, including tumorigenesis, changes in the tumor microenvironment, and metastasis. SOX5 is a member of SOX Group D of Sox family. SOX5 is expressed in various tissues of human body and participates in various physiological and pathological processes and various cellular processes. However, the abnormal expression of SOX5 is associated with cancer of various systems, and the abnormal expression of SOX5 acts as a tumor promoter to promote cancer cell viability, proliferation, invasion, migration and EMT through multiple mechanisms. In addition, the expression pattern of SOX5 is closely related to cancer type, stage and adverse clinical outcome. Therefore, SOX5 is considered as a potential biomarker for cancer diagnosis and prognosis. In this review, the expression of SOX5 in various human cancers, the mechanism of action and potential clinical significance of SOX5 in tumor, and the therapeutic significance of Sox5 targeting in cancer were reviewed. In order to provide a new theoretical basis for cancer clinical molecular diagnosis, molecular targeted therapy and scientific research.

Keywords: SRY associated high mobility population box 5 (SOX5); biomarker; cancer; oncogene; targeted therapy.

Figure 1

SOX family and SOX5 gene. (A) Representative protein structures of SOX family members from groups A to H Top from left to right: SOX family, representative members, n-terminal, C-terminal. In the bottom box, each subfamily represents the individual domains of the protein. (B) The SOX5 gene is located on chromosome 12q12.12 and contains 3 transcripts: NM_006940.6, NM_152989.5 and XM_0024449159.2.

Figure 2

The expression of SOX5 in various tumors was different from that in normal tissues. (Data from GEPIA (Gene Expression Profiling Interactive Analysis). N, Normal tissue; T, tumor tissue; ACC, adrenocortical cancer; BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; CESC, cervical & endocervical cancer; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma; DLBC, diffuse large B-cell lymphoma; ESCA, esophageal carcinoma; GBM, glioblastoma multiforme; HNSC, head & neck squamous cell carcinoma; KICH, kidney chromophobe; KIRC, kidney clear cell carcinoma; KIRP, kidney papillary cell carcinoma; LAML, acute myeloid leukemia; LGG, brain lower grade glioma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; MESO, mesothelioma; OV, ovarian serous cystadenocarcinoma; PAAD, pancreatic adenocarcinoma; PCPG, pheochromocytoma & paraganglioma; PRAD, prostate adenocarcinoma; READ, rectum adenocarcinoma; SARC, sarcoma; SKCM, skin cutaneous melanoma; STAD, stomach adenocarcinoma; TGCT, testicular germ cell tumor; THCA, thyroid carcinoma; THYM, thymoma; UCEC, uterine corpus endometrioid carcinoma; UCS, uterine carcinosarcoma; UVM, uveal melanoma. The abbreviation written in green indicates that the expression of SOX5 is higher in normal tissue of this tumor than in cancerous tissue.

Figure 3

Mechanism of action of SOX5 in cancer.