Hypermethylation of the CHRDL1 promoter induces proliferation and metastasis by activating Akt and Erk in gastric cancer

Abstract

CHRDL1 (Chordin-like 1) is a secreted protein that acts as an antagonist of bone morphogenetic protein (BMP). BMP plays a role as an activator of BMP receptor II (BMPR II), which mediates extracellular to intracellular signal transmission and is involved in carcinogenesis and metastasis. Herein, we report that CHRDL1 expression was significantly down-regulated in gastric cancer tissues and associated with poor survival. Clinic-pathological parameters demonstrated a close relationship between low CHRDL1 expression and metastasis. In vitro, CHRDL1 knockdown promoted tumor cell proliferation and migration through BMPR II by activating Akt, Erk and β-catenin. Furthermore, we observed the hypermethylation of the CHRDL1 promoter in gastric cancer, which induced low expression of CHRDL1 and decreased its secretion to the supernatant. Finally, in vivo experiments confirmed that CHRDL1 acted as a tumor suppressor gene in suppressing tumor growth and metastasis.

Comprehensive Analysis of the Characteristics and Differences in Adult and Newborn Brown Adipose Tissue (BAT): Newborn BAT Is a More Active/Dynamic BAT

“…Another downstream lncRNA at the core of the interaction network is NONMMUG004953, and the expression of some mRNAs related to T cell function (Mr1) [61] and inflammation (NAAA) [62] was altered. There are three lncRNAs located close together in the interaction network: NONMMUG034109, NONMMUG021221, and NONMMUG008287; these are involved in the regulation of the mRNA expression of a large number of cancer-related genes, such as Pik3r1, Gulp1, Chrdl1, and Crebaf [63][64][65][66]. These phenomena suggest that BAT may be closely related to cancer, which coincides with the results of the RNA-Seq ( Figures S2 and S3), and may provide an extremely novel approach for the treatment of cancer.…”

TCGA dataset‑based construction and integrated analysis of aberrantly expressed long non‑coding RNA mediated competing endogenous RNA network in gastric cancer

“…Certain lncRNAs that exist in the network have been proven to interact with miRNA and mRNA and may be potential biomarkers in the diagnosis, therapy and prognosis of GC, including UCA1, HOTTIP, HOTAIR and H19 (45)(46)(47)(48). Additionally, a few genes from the ceRNA network, including CHRDL1, COL1A1, HOXC8 and ATAD2, have been reported to act as tumor oncogenes or suppressor genes, participating in tumor growth, invasion and metastasis (41,(49)(50)(51).…”

Unique transcriptomic landscapes identified in idiopathic spontaneous and infection related preterm births compared to normal term births

“…191 TNC, C3, CP, MELTF, and CHRDL1 upregulation maybe due to the activation of RAS signaling 192 through either the IGF signaling pathway [12], or possibly through IGFBP2 activation of EGFR or cytokine 193 activation of growth factor signaling. TNC, C3, CP represent inflammatory markers [28][29][30][31], while CHRDL1 194 is a marker of cellular aging and BMP4 agonist, likely signaling the arrest of BMP4 related cell proliferation 195 [32,33]. TNC and C3 are of particular interest due to their roles in physiological processes central to placental 196 maturation.…”