Novel miR-5582-5p functions as a tumor suppressor by inducing apoptosis and cell cycle arrest in cancer cells through direct targeting of GAB1, SHC1, and CDK2

Abstract

MicroRNAs (miRNAs) play pivotal roles in tumorigenesis as either tumor suppressors or oncogenes. In the present study, we discovered and demonstrated the tumor suppressive function of a novel miRNA miR-5582-5p. miR-5582-5p induced apoptosis and cell cycle arrest in cancer cells, but not in normal cells. GAB1, SHC1, and CDK2 were identified as direct targets of miR-5582-5p. Knockdown of GAB1/SHC1 or CDK2 phenocopied the apoptotic or cell cycle arrest-inducing function of miR-5582-5p, respectively. The expression of miR-5582-5p was lower in tumor tissues than in adjacent normal tissues of colorectal cancer patients, while the expression of the target proteins exhibited patterns opposite to that of miR-5582-5p. Intratumoral injection of a miR-5582-5p mimic or induced expression of miR-5582-5p in tumor cells suppressed tumor growth in HCT116 xenografts. Collectively, our results suggest a novel tumor suppressive function for miR-5582-5p and its potential applicability for tumor control.

Investigating potential molecular mechanisms of serum exosomal miRNAs in colorectal cancer based on bioinformatics analysis

“…[ 72 ] In recent years, studies have shown that miRNAs regulate cell proliferation, cell migration, and angiogenesis in colorectal cancer by targeting Src. [ 73 – 75 ] In this study, miR-141 significantly reduced in serum exosomes of colorectal cancer and Src was predicted as a target gene of miR-141. Therefore, we speculated that miR-141 may play a role as a tumor suppressor via targeting Src gene in CRC.…”

Inhibition of microRNA-29a alleviates hyperoxia-induced bronchopulmonary dysplasia in neonatal mice via upregulation of GAB1

“…The protein expression level of CD31 has been detected to be decreased in the BPD group (Wang et al 2014), a finding of which was similar to ours: the positive expression rate of CD31 protein displayed a notable decline in lung tissues of neonatal mice with hyperoxia-induced BPD. miR-29b leads to retarded growth of intestinal epithelial cells and suppressing GAB1 expression induces apoptosis (An et al 2016). In addition, decreased miR-29a-3p expression gives rise to enhanced proliferation of glioma cells via the upregulation of GAB1 (Shao et al 2018).…”

Gab3 is required for human colorectal cancer cell proliferation

“…Activation of these oncogenic signalings is important for CRC cell progression [1,8,9]. Recent studies have focused on expression and potential functions of Gab1, the most dominant Gab family protein, in CRC [10,28,29]. It has been shown that Gab1 is over-expressed and/or over-activated in CRC, which is associated with cancer cell progression [10,28,29].…”

“…Recent studies have focused on expression and potential functions of Gab1, the most dominant Gab family protein, in CRC [10,28,29]. It has been shown that Gab1 is over-expressed and/or over-activated in CRC, which is associated with cancer cell progression [10,28,29]. For example, An et al, showed that miR-5582-5p selectively degrades Gab1 to inhibit CRC cells [29].…”

“…It has been shown that Gab1 is over-expressed and/or over-activated in CRC, which is associated with cancer cell progression [10,28,29]. For example, An et al, showed that miR-5582-5p selectively degrades Gab1 to inhibit CRC cells [29]. Similarly, Bai et al, showed that microRNA-409-3p inhibits CRC cell invasion and metastasis possibly via depleting Gab1 [28].…”