SALL4 and microRNA: The Role of Let-7

Abstract

SALL4 is a zinc finger transcription factor that belongs to the spalt-like (SALL) gene fam-ily. It plays important roles in the maintenance of self-renewal and pluripotency of embryonic stem cells, and its expression is repressed in most adult organs. SALL4 re-expression has been observed in different types of human cancers, and dysregulation of SALL4 contributes to the pathogenesis, metastasis, and even drug resistance of multiple cancer types. Surprisingly, little is known regard-ing how SALL4 expression is controlled, but recently microRNAs (miRNAs) have emerged as im-portant regulators of SALL4. Due to the ability of regulating targets differentially in specific tissues, and recent advances in systemic and organ specific miRNA delivery mechanisms, miRNAs have emerged as promising therapeutic targets for cancer treatment. In this review, we summarize cur-rent knowledge of the interaction between SALL4 and miRNAs in mammalian development and cancer, paying particular attention to the emerging roles of the Let-7/Lin28 axis. In addition, we discuss the therapeutic prospects of targeting SALL4 using miRNA-based strategies, with a focus on the Let-7/LIN28 axis.

SALL4: An Intriguing Therapeutic Target in Cancer Treatment

“…Mir-107 also inhibits SALL4 expression in glioma cells [ 29 ]. There are several other miRNAs that their regulatory effect on SALL4 has been identified, which have extensively been discussed in our previous review article [ 30 ].…”

SALL Proteins; Common and Antagonistic Roles in Cancer

“…More specifically for SALL4, miR-16 is common in glioma and gastric cancer, miR-103 in glioma and oral squamous cell carcinoma, and miR-107 in glioma and osteosarcoma. For more comprehensive information on SALL4 and miRNAs and the strategies targeting the miR/SALL4 axis in cancer, see a recent review by Liu J and collaborators [ 100 ].…”

“…The use of miRNAs targeting SALL4-associated HCC has also been proposed. Let-7/miR-98-induced SALL4 depletion decreased the expression of MMP2/9, Fibronectin, n -cadherin, and increased E-cadherin, which correlated with reduced migration/invasion and EMT in an HCC in vivo cancer model [ 100 ].…”

“…This evidence suggests that the SALL status is a valuable tool for predicting the response to chemotherapeutic drugs and other cancer treatments in various malignancies [ 54 , 55 , 92 , 94 , 95 , 96 , 97 , 145 , 168 , 181 , 189 ]. On the contrary, SALL4 promoter hypomethylation and miRNAs-dependent SALL4 regulation are common events in several cancer types [ 98 , 99 , 100 ]. Likewise, studies indicate that the oncogenic function of SALL4 and the tumor suppressor function of SALL1 greatly rely on the recruitment of the NuRD complex.…”

“…SALL1–3 promoters are hypermethylated in several cancers [ 54 , 55 , 92 , 93 , 94 , 95 , 96 , 97 ]. In contrast, the SALL4 promoter is hypomethylated in AML and MDS [ 98 , 99 ] and regulated by miRNAs in multiple cancer types [ 100 ]. Additionally, SALL1 and SALL2 are regulated by miRs ( Table 1 ).…”