LncRNA testis-specific transcript, Y-linked 15 (TTTY15) promotes proliferation, migration and invasion of colorectal cancer cells via regulating miR-29a-3p/DVL3 axis

Abstract

BACKGROUND: Long non-coding RNA testis-specific transcript, Y-linked 15 (TTTY15) is oncogenic in prostate cancer, however its expression and function in colorectal cancer remain largely unknown. METHODS: Paired colorectal cancer samples/adjacent tissues were collected, and the expression levels of TTTY15, miR-29a-3p and disheveled segment polarity protein 3 (DVL3) were examined by quantitative real-time polymerase chain reaction (qRT-PCR); TTTY15 shRNA and overexpression plasmids were transfected into HT29 and HCT-116 cell lines using lipofectamine reagent, respectively; the proliferation and colony formation were detected by CCK-8 assay and plate colony formation assay; qRT-PCR and Western blot were used to analyze the changes of miR-29a-3p and DVL3; dual-luciferase reporter gene assay was used to determine the regulatory relationships between miR-29a-3p and TTTY15, miR-29a-3p and DVL3. RESULTS: TTTY15 was significantly up-regulated in cancerous tissues of colorectal cancer samples, positively correlated with the expression of DVL3, while negatively correlated with the expression of miR-29a-3p. After TTTY15 shRNAs were transfected into colorectal cancer cells, the proliferation and metastasis of cancer cells were significantly inhibited, while TTTY15 overexpression had opposite biological effects. TTTY15 shRNA could reduce the expression of DVL3 on both mRNA and protein levels, and the luciferase activity of TTTY15 sequence was also inhibited by miR-29a-3p. DVL3 was also validated as a target gene of miR-29a-3p, and it could be repressed by miR-29a-3p mimics or TTTY15 shRNA. CONCLUSION: TTTY15 is abnormally upregulated in colorectal cancer tissues, and it can modulate the proliferation and metastasis of colorectal cancer cells. It functions as the ceRNA to regulate the expression of DVL3 by sponging miR-29a-3p.

Protein tyrosine kinase 7‑knockdown inhibits oral squamous cell carcinoma cell viability, proliferation, migration and invasion via downregulating dishevelled segment polarity protein 3 expression

“…In addition, the knockdown of DVL3 expression has been found to control the progression of esophageal squamous cell carcinoma, inhibit cell proliferation and promote the apoptosis of tumor cells (27). Moreover, a recent study has revealed that testis-specific transcript, Y-linked 15 downregulates DVL3 expression in colorectal cancer tissues and promotes the proliferation, migration and invasion of colorectal cancer cells (32). The findings of the present study revealed that the expression levels of DVL3 were upregulated in OSCC cell lines, and a Co-IP assay confirmed Figure 5.…”

Human MicroRNAs Interacting With SARS-CoV-2 RNA Sequences: Computational Analysis and Experimental Target Validation

“…Intriguingly, miR-30c has also been involved in the infection by Porcine epidemic diarrhea virus (PEDV), a member of the Alphacoronavirus family: the virus engages the SOCS1/miR-30c axis to escape IFN-l-mediated antiviral immune responses ( Wang C. et al, 2020 ). miR-29a-3p is involved in gastric and breast cancer, as well as colorectal cancer and hepatocarcinoma ( Li Y. et al, 2020 ; Wang J. et al, 2020 ; Zheng et al, 2020 ; Pan et al, 2021 ; Qu et al, 2021 ); interestingly, miR-29a has been considered as a potential therapeutic target for HIV eradication, because of its binding to Nef viral protein, critical for viral persistence and release, and binding to the 3′UTR region of the HIV genome, mediating the transport of the virus to P-bodies ( Ahluwalia et al, 2008 ; Nathans et al, 2009 ). MiR-15b is probably one of the most extensively studied in relation to cancer pathways, since it shares most of its sequence, including the seed region, with the well-known miR-15a that together with the clustered miR-16 were the first miRNAs related to a tumor, the chronic lymphocytic leukemia ( Calin et al, 2002 ); recently, both loci, miR-15a/16-1 and miR-15b/16-2, have been shown to drive the pathogenesis of acute myeloid leukemia ( Lovat et al, 2020 ).…”

Male-specific long non-coding RNA testis-specific transcript, Y-linked 15 promotes gastric cancer cell growth by regulating Wnt family member 1/β-catenin signaling by sponging microRNA let-7a-5p

“…For example, knocking down TTTY15 reduces H 2 O 2 -induced cardiomyocyte injury via modulating the miR-98-5p/CRP axis [ 29 ]; TTTY15 can promote hypoxia-induced vascular endothelial cell injury by down-regulating miR-186-5p [ 30 ]. Importantly, TTTY15 is also involved in regulating the proliferation, differentiation, apoptosis and other biological processes of cancer cells [ 9 , 11 , 31 ]. Our previous study reports that TTTY15 up-regulates disheveled segment polarity protein 3 (DVL3) expression by adsorbing miR-29a-3p, thus promoting the malignancy of colorectal cancer cells [ 11 ].…”

“…Importantly, TTTY15 is also involved in regulating the proliferation, differentiation, apoptosis and other biological processes of cancer cells [ 9 , 11 , 31 ]. Our previous study reports that TTTY15 up-regulates disheveled segment polarity protein 3 (DVL3) expression by adsorbing miR-29a-3p, thus promoting the malignancy of colorectal cancer cells [ 11 ]. Another study reports that TTTY15 promotes CDK6 and FN1 expressions by adsorbing let-7, therefore promoting PCa cell proliferation [ 9 ].…”