CircRNA circSTIL inhibits ferroptosis in colorectal cancer via miR‐431/SLC7A11 axis

Abstract

Ferroptosis is an emerging programmed cell death and plays essential roles in tumorigenesis, including colorectal cancer (CRC). The present study intended to disclose the role of a novel oncogene circular RNA (circRNA) circSTIL in CRC phenotypes, especially ferroptosis. The expression of circSTIL was measured in CRC tissues and cells.Then, the impacts of circSTIL expression on the proliferation and ferroptosis of CRC cells were examined by loss-of-function assays in vitro. Bioinformatics, luciferase reporter assay and cell rescue assay were further performed to reveal the ceRNAassociated mechanism of circSTIL. CircSTIL was significantly upregulated in CRC. Cell proliferation was suppressed while ferroptosis was induced with the silencing of cir-cSTIL in CRC cells. Interestingly, circSTIL competed with miR-431 for solute carrier family 7 member 11 (SLC7A11) binding. Additionally, miR-431 suppression or SLC7A11 overexpression overturned circSTIL silencing-mediated cell phenotypes in CRC cells. CircSTIL promotes CRC cell proliferation and suppresses ferroptosis in vitro via miR-431/SLC7A11 signaling, revealing the pathogenesis of CRC, and providing potential therapeutic targets of CRC.

Competing endogenous RNA networks and ferroptosis in cancer: novel therapeutic targets

“… Ovarian cancer [ 144 ] CircSTIL/miR-431/SLC7A11 Negative CircSTIL sponges miR-431, leading to SLC7A11 upregulation. Colorectal cancer [ 145 ] Circ_0067934/miR-545-3p/SLC7A11 Negative Circ_0067934 sponges miR-545-3p, leading to SLC7A11 upregulation. Thyroid cancer [ 146 ] CircEPSTI1/miR-375_miR409-3P_miR-515-5p/SLC7A11 Negative CircEPSTI1 sponges miR-375, miR409-3P, and miR-515-5p, leading to SLC7A11 upregulation.…”

“…As an upregulated circRNA in chemoresistant ovarian cancer tissues compared to sensitive ones, circSnx12 knockdown enhances the chemosensitivity and increases apoptosis and ferroptosis of cisplatin chemoresistant ovarian cancer cells circSnx12/miR-194-5p/SLC7A11 axis [ 144 ]. CircSTIL is an increased circRNA in colorectal cancer, and its knockdown is associated with decreased proliferation and enhanced ferroptosis of colorectal cancer cells via the circSTIL/miR-431/SLC7A11 axis [ 145 ]. In thyroid cancer, circ_0067934 knockdown decreases proliferation and increases apoptosis and ferroptosis of malignant cells via the circ_0067934/miR-545-3p/SLC7A11 axis [ 146 ].…”

Ferroptosis-associated circular RNAs: Opportunities and challenges in the diagnosis and treatment of cancer

“…Knockdown of circSTIL induces cellular Fe2+ and lipid ROS accumulation, activates cellular ferroptosis, and inhibits colorectal cancer cell proliferation. In addition, circSTIL targets SLC7A11 by competitively binding to miR-431 to regulate ferroptosis, providing a new target for the treatment of colorectal cancer ( Li et al, 2023 ).…”

The identification and functional analysis of CircRNAs in endometrial receptivity of mice with polycystic ovary

“…Recent evidence demonstrates that circRNAs have multiple biological functions, including cis‐acting regulation of host gene expression, regulation of miRNA target genes by acting as miRNA sponges, protein translation, and protein interaction 14 . CircRNAs have been implicated in a variety of pathological and physiological processes, including various types of malignant cancer, cardiovascular disease, and endocrine dysfunctions 13,15–17 . Recent research has demonstrated that circRNA is essential for developing endometrial receptivity and embryo implantation.…”

“…14 CircRNAs have been implicated in a variety of pathological and physiological processes, including various types of malignant cancer, cardiovascular disease, and endocrine dysfunctions. 13,[15][16][17] Recent research has demonstrated that circRNA is essential for developing endometrial receptivity and embryo implantation. Song et al discovered that several circRNAs were differentially expressed in the endometrium of dairy goats and suggested that circRNAs may be potential regulators of receptive endometrium.…”