miR‐377‐3p drives malignancy characteristics via upregulating GSK‐3β expression and activating NF‐κB pathway in hCRC cells

Abstract

MicroRNA (miRNA) dysregulation has been associated with carcinogenesis in many cancers, including human colorectal cancer (hCRC). However, the effect and mechanism of miR-377-3p on CRC remains elusive. Herein, we first found that miR-377-3p was upregulated in CRC tissues and promoted tumorigenic activity by accelerating the G -S phase transition, promoting cell proliferation and epithelial-mesenchymal transition (EMT) while repressing apoptosis in CRC cells. Glycogen synthase kinase-3β (GSK-3β) was a direct target of miR-377-3p, and upregulated by miR-377-3p. Knockdown of GSK-3β partly rescued miR-377-3p-mediated malignancy characteristics. Most importantly, we showed that miR-377-3p promoted carcinogenesis by activating NF-κB pathway. Taken together, our results first reported that miR-377-3p functions as an oncogene and promotes carcinogenesis via upregulating GSK-3β expression and activating NF-κB pathway in hCRC cells.

LncRNA BDNF‐AS suppresses colorectal cancer cell proliferation and migration by epigenetically repressing GSK‐3β expression

“…It is noteworthy that EZH2 has been reported to downregulate the level of GSK‐3β gene expression through H3K27me3 in the GSK‐3β promoter . In our study, we found a significantly higher level of GSK‐3β levels in CRC tissues compared with adjacent normal tissues and cell lines, which was consistent with the previous studies . In addition, we observed that GSK‐3β mRNA and protein levels were markedly decreased due to lncRNA BDNF‐AS overexpression in vitro.…”

“…11 In our study, we found a significantly higher level of GSK-3β levels in CRC tissues compared with adjacent normal tissues and cell lines, which was consistent with the previous studies. 5,21,22 In addition, we observed that GSK-3β mRNA and protein levels were markedly decreased due to lncRNA BDNF-AS overexpression in vitro. In contrast, GSK-3β mRNA and protein levels were significantly increased by transfection of si-BDNF-AS.…”

“…The glycogen synthase kinase‐3 (GSK‐3) family kinases are a series of highly conserved serine/threonine protein kinases involved in a diverse range of cellular functions, including cell proliferation, migration, invasion, and apoptosis . GSK‐3β is a recently identified family member that functioned as a novel transcriptional activator and a broad oncogene in various types of human cancers, including CRC …”

“…4 GSK-3β is a recently identified family member that functioned as a novel transcriptional activator and a broad oncogene in various types of human cancers, including CRC. 5 Long noncoding RNAs (lncRNAs) are a novel class of RNA transcripts longer than 200 nucleotides with narrow protein coding functions. Emerging data have revealed that lncRNAs play important roles in the occurrence and development of tumours via epigenetic regulation such as DNA methylation, histone modification, and chromatin remodelling.…”

RETRACTED ARTICLE: Mirt2 functions in synergy with miR-377 to participate in inflammatory pathophysiology of Sjögren's syndrome

“…Increasing evidence have elucidated that miRs are associated with inflammation in SS patients [9][10][11]. Besides, miR-377 has been found to mediate the proliferation and apoptosis progresses as well as DNA methylation in several malignancies [12][13][14]. Its modulatory functions on inflammation have been revealed in recent studies [15,16].…”