CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis

Abstract

Background The aim of this study was to investigate the circ_0004370 expression in EC, its effects on cell proliferation, apoptosis, migration, invasion, and epithelial–mesenchymal transition (EMT) process, and the underlying regulatory mechanisms in EC. Methods The protein levels of COL1A1 and EMT-related proteins were detected by western blot. The role of circ_0004370 on cell viability, proliferation, and apoptosis was analyzed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and flow cytometry, respectively. The transwell assay was used to examine cell migration and invasion. The binding sites between miR-1301-3p and circ_0004370 or COL1A1 were predicted by starbase software and confirmed by dual-luciferase reporter assay and RNA pull-down assay. Results We discovered that circ_0004370 was remarkably upregulated in EC tissues and cells. Knockdown of circ_0004370 inhibited cell proliferation, migration as well as invasion, and promoted apoptosis in vitro, while its effect was rescued by miR-1301-3p inhibition. And circ_0004370 mediated the EMT process in EC cells. Moreover, we explored its regulatory mechanism and found that circ_0004370 directly bound to miR-1301-3p and COL1A1 was verified as a target of miR-1301-3p. COL1A1 was highly expressed in EC cells and upregulation of COL1A1 reversed the effects of miR-1301-3p on cell proliferation, migration, invasion, and apoptosis. In addition, silencing of circ_0004370 reduced tumor volumes and weights in vivo. We showed that circ_0004370/miR-1301-3p/COL1A1 axis played the critical role in EC to regulate the cell activities. Conclusion Circ_0004370 promotes EC proliferation, migration and invasion, and EMT process and suppresses apoptosis by regulating the miR-1301-3p/COL1A1 axis, indicating that circ_0004370 may be used as a potential therapeutic target for EC.

RETRACTED ARTICLE: Has_circ_0008583 modulates hepatocellular carcinoma progression through the miR-1301-3p/METTL3 pathway

“…Studies have shown that miR-1301-3p plays a dual role in tumor progression and can be used as a prognostic biomarker and therapeutic target for some malignant tumors [ 21–24 ]. In addition, miR-1301-3p was sponged by Circ_0004370, CircRNA MYLK and participated in cancer progression [ 25 , 26 ]. Here, our results showed that miR-1301-3p mimic could partially reverse the effect of hsa_circ_0008583 overexpression on HCC cell progression, which indicated that hsa_circ_0008583 played a carcinogenic role in HCC by sponging miR-1301-3p.…”

Identification of key genes associated with esophageal adenocarcinoma based on bioinformatics analysis

“…A recent study has demonstrated that COL1A1 and COL4A1 are associated with several clinical parameters, including TNM staging, lymph node metastasis, and tumor invasion depth in gastric cancer patients (48). COL1A1 has been reported to be highly expressed in EC cells, and upregulation of COL1A1 has been associated with cell proliferation, invasion, and apoptosis (49). DCN, a small stromal proteoglycan, is a member of the SLRP gene family (50), and Bozoky et al found that its expression is consistently decreased in the tumor microenvironment of various cancers (51).…”

Aberrant Expression of miR-1301 in Human Cancer

“…miR-1301 is involved in the biological processes of tumor cell proliferation, migration, invasion, and apoptosis by regulating multiple downstream genes (Figure 1). In all tumor types involved in miR-1301, the abnormal expression of miR-1301 can affect the proliferation of tumor cells by affecting cell cycle and apoptosis (1,7,9,12,16,17,24,(26)(27)(28)(29)(33)(34)(35)(36). Metastasis is characterized by cancer cells invading the basement membrane into the adjacent matrix, then invading and surviving into the circulatory system (including blood and lymphatic tissue), and extravasation to distant tissues.…”

“…In cervical cancer, circRNA MYLK up-regulates the expression of RHEB through sponging miR-1301 and promotes tumorigenesis (33). In esophageal cancer, Circ_0004370 up-regulates COL1A1 through sponging miR-1301 to promote the occurrence and development of esophageal cancer (12). In esophageal squamous cell carcinoma (ESCC), SOX2 binds to the MIAT promoter region to promote CircRNA and lncRNA can be used as the ceRNA of miR-1301, which promotes the expression of downstream target genes through sponging miR-1301, and participates in the occurrence and development of tumors.…”