Identification and validation of a miRNA-related expression signature for tumor mutational burden in colorectal cancer

Background MicroRNAs play an important role in the genesis and progression of tumours, including colorectal cancer (CRC), which has a high morbidity and mortality rate. In this research, the role of miR-495-3p and HMGB1 in CRC was investigated. Methods We performed qRT-PCR to detect the expression of miR-495-3p in colorectal cancer tissues and cell lines. Functional experiments, such as CCK-8, EdU, Transwell and apoptosis assays, were conducted to explore the effects of miR-495-3p on the proliferation, migration and apoptosis of CRC cells in vitro. Then, database prediction, dual-luciferase reporter gene assays and functional experiments verified the role of the miR-495-3p target gene HMGB1 in CRC. Finally, rescue experiments were performed to investigate whether overexpression of HMGB1 could reverse the inhibitory effect of miR-495-3p on CRC cell proliferation in vivo and in vitro. Results miR-495-3p was downregulated in colorectal cancer tissues and cell lines, inhibited the proliferation and migration of colorectal cancer cells and promoted cell apoptosis. Database prediction and dual-luciferase reporter gene assays showed that HMGB1 was the downstream target gene of miR-495-3p. We finally demonstrated that miR-495-3p inhibited CRC cell proliferation by targeting HMGB1 in vitro and in vivo. Conclusion Our research shows that miR-495-3p inhibits the progression of colorectal cancer by downregulating the expression of HMGB1, which indicates that miR-495-3p may become a potential therapeutic target for colorectal cancer.

Section: Introductionmentioning

confidence: 99%

miR-495-3p depresses cell proliferation and migration by downregulating HMGB1 in colorectal cancer

Zhang

Zheng

et al. 2022

“…Dysregulation of miRNAs plays an important role in various cancer development and progression, including breast cancer [ 32 , 33 ]. Aberrant expression of miR-381-3p is observed in many types of cancers, suggesting that miR-381-3p might play a crucial role in tumorigenesis and progression [ 13 , 18 , 34 – 36 ].…”

Section: Discussionmentioning

confidence: 99%

miR-381-3p suppresses breast cancer progression by inhibition of epithelial–mesenchymal transition

Ren

et al. 2021

Background Accumulating evidence indicates that miRNAs are involved in multiple cellular functions and participate in various cancer development and progression, including breast cancer. Methods We aimed to investigate the role of miR-381-3p in breast cancer. The expression level of miR-381-3p and EMT transcription factors was examined by quantitative real-time PCR (qRT-PCR). The effects of miR-381-3p on breast cancer proliferation and invasion were determined by Cell Counting Kit-8 (CCK-8), colony formation, and transwell assays. The regulation of miR-381-3p on its targets was determined by dual-luciferase analysis, qRT-PCR, and western blot. Results We found that the expression of miR-381-3p was significantly decreased in breast cancer tissues and cell lines. Overexpression of miR-381-3p inhibited breast cancer proliferation and invasion, whereas knockdown of miR-381-3p promoted cell proliferation and invasion in MDA-MB-231 and SKBR3 cells. Mechanistically, overexpression of miR-381-3p inhibited breast cancer epithelial–mesenchymal transition (EMT). Both Sox4 and Twist1 were confirmed as targets of miR-381-3p. Moreover, transforming growth factor-β (TGF-β) could reverse the effects of miR-381-3p on breast cancer progression. Conclusions Our observation suggests that miR-381-3p inhibits breast cancer progression and EMT by regulating the TGF-β signaling via targeting Sox4 and Twist1.

“…It is worth noting that previous studies have identified multiple lncRNAs and miRNAs with critical functions in EC and other cancers [20][21][22][23][24][25][26]. Future studies should focus on the clinical applications of these lncRNAs and miRNAs.…”

Section: Discussionmentioning

confidence: 99%

The MCM3AP-AS1/miR-126/VEGF axis regulates cancer cell invasion and migration in endometrioid carcinoma

Fan

2021

Background Long non-coding RNA (lncRNA) MCM3AP-AS1 plays an oncogenic role in several malignancies, but its role in endometrioid carcinoma (EC) is unclear. This study was carried out to explore the role of MCM3AP-AS1 in EC. Methods A total of 60 EC patients were enrolled in this study. Expression levels of MCM3AP Antisense RNA 1 (MCM3AP-AS1), microRNA-126 (miR-126), and vascular endothelial growth factor (VEGF) in tissues and transfetced cells were measured by RT-qPCR. Cell transfections were performed to explore the interaction among MCM3AP-AS1, miR-126 and VEGF. Transwell assays were perfromed to evaluate the invasion and migration abilities of HEC-1 cells after transfection. Results MCM3AP-AS1 was upregulated in EC and predicted poor survival. MCM3AP-AS1 directly interacted with miR-126. In EC cells, overexpression of MCM3AP-AS1 and miR-126 did not significantly affect the expression of each other. In addition, overexpression of MCM3AP-AS1 increased the expression levels of VEGF, a target of miR-126. Moreover, overexpression of MCM3AP-AS1 and VEGF increased the migration and invasion rates of EC cells, while overexpression of miR-126 suppressed these cell behaviors. Overexpression of MCM3AP-AS1 attenuated the role of miR-126 in cell invasion and migration. Conclusions Therefore, MCM3AP-AS1 may serve as a competing endogenous RNA (ceRNA) of miR-126 to upregulate VEGF, thereby regulating cancer cell behaviors in EC.