SHMT2 Drives the Progression of Colorectal Cancer by Regulating UHRF1 Expression.

Ximao Cui,Yun Liu,Chiye Ma,Yanfen Cui,Shun Zhang,Xiaohua Jiang,Yuzhe Gao,Tao Du,Guanghui Wang,Chun Song,Qing Ni

doi:10.1155/2022/3758697

Abstract

Introduction Serine hydroxymethyltransferase 2 (SHMT2) has a critical role in serine-glycine metabolism to drive cancer cell proliferation. Yet, the function of SHMT2 in tumorigenesis, especially in human colorectal cancer (CRC) progression, remains largely unclear. Materials and Methods CRC and paired normal samples were collected in the Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, and assessed by real-time polymerase chain reaction (qPCR) analysis, western blot (WB), and immunohistochemistry (IHC). Moreover, SHMT2 expression in human CRC cells was identified by qPCR and WB. The CRC cell proliferation, migration, and invasion after SHMT2 knockdown were explored through in vitro and in vivo assays. mRNA-seq assays were used to investigate the underlying mechanisms behind the SHMT2 function. Results It was found that SHMT2 mRNA and protein were overexpressed in CRC tissue compared to the levels in normal mucosa. Positive expression of SHMT2 was significantly correlated with TNM stage and lymph node metastasis, and elevated expression of SHMT2 resulted as an independent prognostic factor in patients with CRC. SHMT2 knockdown impaired the proliferation of CRC in vitro and in vivo and induced cell cycle arrest by regulating UHRF1 expression. Conclusion Taken together, our findings reveal that UHRF1 is a novel target gene of SHMT2, which can be used as a potential therapeutic strategy for CRC therapy.

Highlights

Serine hydroxymethyltransferase 2 (SHMT2) has a critical role in serine-glycine metabolism to drive cancer cell proliferation
SHMT2 Is Highly Expressed in Tumor Tissues from colorectal cancer (CRC) Patients
Among serine hydroxymethyltransferase (SHMT) family members, SHMT2 was markedly upregulated in CRC tissues, whereas the expression of SHMT1 did not significantly change (Figure S1A)

Summary

Introduction

Colorectal cancer (CRC) is the third most common cancer, accounting for 10% of all cancer cases worldwide. Relevant studies have shown that SHMT2 (serine hydroxymethyltransferase 2), a key enzyme of serine metabolism, is involved in the occurrence and development of tumors and in the regulation of tumor cell proliferation [5]. With the continuous in-depth study of tumor metabolism mechanisms, a series of metabolism-related enzymes and molecules, including the expression and function of serine hydroxymethyltransferase (SHMT), have been found to be involved in the occurrence and development of tumors. One-carbon unit metabolism driven by serine has been identified as an important pathway for the production of NADPH [16] as SHMT2 is regarded as an essential gene in the process of tumorigenesis and development, and a variety of tumors have been confirmed to be related to it [17,18,19,20]. We detected the expression of SHMT2 protein in colorectal cancer tissues and compared it with the corresponding normal tissues to analyze its relationship with the clinicopathological characteristics and prognosis of colorectal cancer. e mechanism of SHMT2 in colorectal cancer cell lines was discussed

Results

56 KDa β-ACTIN

56 KDa beta-ACTIN sh1

Materials and Methods