circ_LRIG3 contributes to the progression of hepatocellular carcinoma by elevating RNF38 via sponging miR-449a

Abstract

Circular RNAs (circRNAs) play crucial roles in multiple cancers, including hepatocellular carcinoma (HCC). However, the effects and molecular mechanisms of circ_LRIG3 in HCC remain barely unknown. qRT-PCR assay was employed to detect the levels of circ_LRIG3, LRIG3, miR-449a and ring finger protein 38 (RNF38). RNase R assay and Actinomycin D assay were performed to analyze the characteristics of circ_LRIG3. Colony formation assay and MTT assay were used to evaluate cell proliferation. Flow cytometry analysis and transwell assay were adopted for cell apoptosis and metastasis, respectively. Western blot assay was carried out for the protein levels of Ki67, Snail, E-cadherin, RNF38, Smad2/3 and p-Smad2/3. Murine xenograft model assay was used to explore the role of circ_LRIG3 in vivo. circ_LRIG3 expression was upregulated in HCC tissues and cells. Knockdown of circ_LRIG3 suppressed proliferation, migration and invasion and facilitated cell apoptosis in HCC cells in vitro and blocked tumor growth of HCC in vivo. RNF38 overexpression reversed the effects of circ_LRIG3 knockdown on the malignant behaviors of HCC cells. Moreover, circ_LRIG3 could sponge miR-449a to positively modulate RNF38 expression in HCC cells. circ_LRIG3 knockdown inhibited the progression of HCC cells by sponging miR-449a. In addition, circ_LRIG3 silencing might inhibit the Smad2/3 pathway. circ_LRIG3 facilitated HCC progression by modulation of miR-449a/LRIG3 axis, which might provide a novel method for HCC therapy.

Hepatocellular Carcinoma: Up-regulated Circular RNAs Which Mediate Efficacy in PreclinicalIn VivoModels

“…In addition to ubiquitinylation of p53, as outlined previously (110), UBE-2T can promote HCC carcinogenesis via cellcycle promotion and inhibition of apoptosis (113). 3A) was upregulated in HCC (114). Knockdown of circLRIG3 suppressed proliferation, migration, invasion and facilitated apoptosis of HCC cells in vitro and blocked growth of HCC xenografts in nude mice.…”

Lrig3 restricts the size of the colon stem cell compartment

“…Using human colon cancer cell lines, Zang and colleagues were able to show that Lrig3 represses metastasis-associated cell motility by inhibiting slug via inactivating ERK signaling (29). While the data on Lrig3 expression in solid tumors is expanding rapidly (5, 6, 12, 17, 23, 24, 29), the role of Lrig3 in the gastrointestinal tract at the genome, transcriptional and protein level is largely unknown and represents a valuable avenue for future research for both normal and cancerous colon tissue.…”

“…Detection of blood plasma circ-Lrig3 is a highly sensitive and specific diagnostic indicator for HCC (23). Mechanistically, downregulation of circRNA Lrig3 represses both the MAPK/ERK and Smad pathways to prevent the progression of HCC and the loss of circRNA Lrig3 suppresses proliferation, invasion of HCC cells in vitro and blocks tumor growth of HCC in vivo (12, 24). One recent report gives us a glimpse of the potential role in advanced colon cancer.…”

“…The copyright holder for this preprint this version posted March 12, 2022. ; https://doi.org/10.1101/2022.03.08.483523 doi: bioRxiv preprint cell types: cervical, hepatocellular, prostate, glioblastoma and colon (5,6,12,17,23,24,28).…”

“…Generally, mice, sheep and pig are smaller if they have a loss-of-function in Lrig3 (1, 11, 15). Only recently have contributions to primary literature uncovered mechanistic roles for Lrig3 in the progression of many cancer cell types: cervical, hepatocellular, prostate, glioblastoma and colon (5, 6, 12, 17, 23, 24, 28).…”