circCOL1A1 Promotes the Progression of Gastric Cancer Cells through Sponging miR-145 to Enhance RABL3 Expression

Abstract

Circular RNA has been reported to be a new noncoding RNA which plays important roles in tumor progression. One of the most common functions of circular RNA is to regulate microRNA expression by acting as a microRNA sponge. However, the circular RNA expression profile and function remain mostly unclear in gastric cancer. In the study, we explored the expression and function of circCOL1A1 (hsa_circ_0044556) in gastric cancer. We performed RT-PCR with divergent primers, mRNA stability assay, and RNase R digestion assay to characterize circCOL1A1 in gastric cancer cell lines. qRT-PCR was applied to detect the level of circCOL1A1 in both gastric cancer cell lines and tissues. Gain- and loss-of-function studies were carried out to detect the influence of circCOL1A1 on gastric cancer cells by performing CCK8, migration, and invasion assays. The regulation of the downstream genes was identified by qRT-PCR, western blot assay, dual luciferase assay, and RNA pull-down assay. The results showed that circCOL1A1 was highly expressed in both gastric cancer cells and tissues. Silence of circCOL1A1 inhibited the proliferation, migration, and invasion of gastric cancer cells. circCOL1A1 regulated the expression of miR-145 by acting as a microRNA sponge, and the influence of circCOL1A1 could be abrogated by miR-145 mimics. Our research shows that miR-145 plays its functions through targeting and regulating RABL3. Inhibition of circCOL1A1/miR-145/RABL3 could effectively suppress gastric cancer cell proliferation, migration, and invasion. circCOL1A1 also promote the transformation of M1 into M2 macrophage. Our study identified circCOL1A1 as a novel oncogenic circRNA and will provide more information for gastric cancer therapy.

Atypical small GTPase RABL3 interacts with RAB11 to regulate early ciliogenesis in human cells

“…While other small RABL proteins localize to the basal body and/or the ciliary axoneme, RABL3 shows a wider distribution throughout cells. Since RABL3 has been shown to pertain to multiple cellular events, including KRAS signaling, lymphopoiesis, and cancer cells proliferation and migration (An et al, 2017; Ge et al, 2019; Li et al, 2010; Ma et al, 2021; Nissim et al, 2019; Pan et al, 2017; Usman et al, 2020; Xu et al, 2021; Zhang et al, 2016; Zhong et al, 2020), RABL3 may be located broadly to play distinct roles depending on target molecules, interacting proteins, and/or cell types.…”

“…RABL proteins are devoid of sites for lipid modification and some conserved residues in GTP-binding proteins (Blacque et al, 2018; Homma et al, 2021). RABL3 is upregulated in several cancers and is required for their proliferation and migration (An et al, 2017; Ge et al, 2019; Li et al, 2010; Ma et al, 2021; Pan et al, 2017; Usman et al, 2020; Xu et al, 2021; Zhang et al, 2016). Mutations in rabl3 are correlated with heritable pancreatic cancer (Nissim et al, 2019).…”

The atypical small GTPase RABL3 interacts with RAB11 to regulate early ciliogenesis in human cells

“…While other small RABL proteins localize to the basal body and/or the ciliary axoneme, RABL3 shows a wider distribution throughout cells. Since RABL3 has been shown to pertain to multiple cellular events, including KRAS signaling, lymphopoiesis, and cancer cells proliferation and migration (An et al, 2017;Ge et al, 2019;Li et al, 2010;Ma et al, 2021;Nissim et al, 2019;Pan et al, 2017;Usman et al, 2020;Xu et al, 2021;Zhang et al, 2016;Zhong et al, 2020), RABL3 may be located broadly to play distinct roles depending on target molecules, interacting proteins, and/or cell types.…”

“…RABL proteins are devoid of sites for lipid modification and some conserved residues in GTP-binding proteins (Blacque et al, 2018;Homma et al, 2021). RABL3 is upregulated in several cancers and is required for their proliferation and migration (An et al, 2017;Ge et al, 2019;Li et al, 2010;Ma et al, 2021;Pan et al, 2017;Usman et al, 2020;Xu et al, 2021;Zhang et al, 2016).…”

Circular RNA 0000654 facilitates the growth of gastric cancer cells through absorbing microRNA-149-5p to up-regulate inhibin-beta A

“…Cell extract (2 μg) was incubated with 100 pmol biotinylated RNA, added with agarose beads (Invitrogen) and detected by RT-qPCR. The experiment was conducted 3 times [ 23 ].…”