CircRNA_101951 promotes migration and invasion of colorectal cancer cells by regulating the KIF3A‑mediated EMT pathway

Li, Yuefeng; Pei, Fulai; Cao, Ming-zheng

doi:10.3892/etm.2020.8600

Cited by 20 publications

(16 citation statements)

References 27 publications

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“…Importantly, circRNAs may regulate the expression of cell cycle-related proteins (e.g., p53 and p16) [ 72 , 125 ], apoptosis-related proteins (e.g., Bax and Bcl-2) [ 97 , 163 ] and EMT-related proteins (e.g., MMP2, MMP-9, and E-cadherin) [ 164 – 166 ] to mediate cell cycle arrest, apoptosis, and EMT. Additionally, circRNAs directly regulate CRC-associated signaling pathways, such as the Wnt/β-catenin pathway [ 76 , 78 , 167 ] and PTEN/Akt/mTOR pathway [ 168 , 169 ].…”

Section: Circrnas and Crcmentioning

confidence: 99%

Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer

et al. 2021

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Colorectal cancer (CRC) is a common hereditary tumor that is often fatal. Its pathogenesis involves multiple genes, including circular RNAs (circRNAs). Notably, circRNAs constitute a new class of noncoding RNAs (ncRNAs) with a covalently closed loop structure and have been characterized as stable, conserved molecules that are abundantly expressed in tissue/development-specific patterns in eukaryotes. Based on accumulating evidence, circRNAs are aberrantly expressed in CRC tissues, cells, exosomes, and blood from patients with CRC. Moreover, numerous circRNAs have been identified as either oncogenes or tumor suppressors that mediate tumorigenesis, metastasis and chemoradiation resistance in CRC. Although the regulatory mechanisms of circRNA biogenesis and functions remain fairly elusive, interesting results have been obtained in studies investigating CRC. In particular, the expression of circRNAs in CRC is comprehensively modulated by multiple factors, such as splicing factors, transcription factors, specific enzymes and cis-acting elements. More importantly, circRNAs exert pivotal effects on CRC through various mechanisms, including acting as miRNA sponges or decoys, interacting with RNA binding proteins, and even translating functional peptides. Finally, circRNAs may serve as promising diagnostic and prognostic biomarkers and potential therapeutic targets in the clinical practice of CRC. In this review, we discuss the dysregulation, functions and clinical significance of circRNAs in CRC and further discuss the molecular mechanisms by which circRNAs exert their functions and how their expression is regulated. Based on this review, we hope to reveal the functions of circRNAs in the initiation and progression of cancer and highlight the future perspectives on strategies targeting circRNAs in cancer research.

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Section: Circrnas and Crcmentioning

confidence: 99%

Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer

et al. 2021

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“…26 CircRNA_101951 accelerates CRC cell migration and invasion through activating the KIF3A-mediated EMT pathway. 27 The results of microarray analysis unveiled that the differential expression of circTADA2A was the most significant in CRC tissues among down-regulated circRNAs. Interestingly, circTADA2A has been testified to exert opposite roles in osteosarcoma and breast cancer.…”

Section: Discussionmentioning

confidence: 99%

circTADA2A Retards the Progression of Colorectal Cancer via Regulating miR-1229/BCL2L10 Signal Axis

Fang

Zhang

et al. 2021

CMAR

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Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related death around the world, becoming a severe public health problem. Mounting evidence has proven that circRNAs act as pivotal modulators in the initiation and development of CRC. Although the function of circTADA2A has been explored in osteosarcoma and breast cancer, the specific role of circTADA2A in CRC remains unknown. Methods: Bioinformatics analysis based on GEO datasets was used to evaluate the dysregulated circRNAs in CRC. CCK-8 and transwell assays were used to detect the functions of CRC cells. qRT-PCR and Western blot were performed to evaluate the expression of RNAs and proteins. Luciferase assay and RNA pull down experiment were carried out to verify the interaction between miR and its targets. Results: CircTADA2A was downregulated in CRC tissues compared with normal samples. CircTADA2A exhibited greater stability than its linear form when exposed to RNase R and actinomycin D treatment. qRT-PCR analysis validated the lower expression level of circTADA2A in CRC. The loss-of-function and gain-of-function assays indicated that circTADA2A exerted the inhibitory role in CRC cell proliferation and migration. Mechanistically, circTADA2A functioned as a sponge of miR-1229. Further experiments manifested that circTADA2A regulated BCL2L10 expression via competitively binding to miR-1229. More importantly, the tumor suppressor role of circTADA2A in the malignant behaviors of CRC cells was mediated by BCL2L10. Conclusion: circTADA2A suppressed cell proliferation and migration in CRC through regulation of miR-1229/BCL2L10 axis, which suggested that circTADA2A might represent a novel potential target for the treatment of CRC.

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“…The above experimental data confirmed that tRF-17-79MP9PP could inhibit breast malignant activities of cancer cells, so its target gene should be associated with tumor cell invasion, metastasis or proliferation. Based on the rationale, four candidate genes (THBS1, KIF3A, RAB10, RFX5) were selected after a literature review (18)(19)(20)(21)(22)(23). Further analysis revealed that tRF-17-79MP9PP had "seed sequences", which may bind to the 3'UTR of the four candidate genes according to TargetScan and miRanda programs (Figure 4B).…”

Section: Go and Kegg Enrichment Analysis Of Trf-17-79mp9pp Target Genesmentioning

confidence: 99%

tRNA-Derived Fragment tRF-17-79MP9PP Attenuates Cell Invasion and Migration via THBS1/TGF-β1/Smad3 Axis in Breast Cancer

Zheng

et al. 2021

Front. Oncol.

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tRNA derivatives have been identified as a new kind of potential biomarker for cancer. Previous studies have identified that there were 30 differentially expressed tRNAs derivatives in breast cancer tissue with the high-throughput sequencing technique. This study aimed to investigate the possible biological function and mechanism of tRNA derivatives in breast cancer cells. One such tRF, a 5’-tRF fragment of tRF-17-79MP9PP (tRF-17) was screened in this study, which is processed from the mature tRNA-Val-AAC and tRNA-Val-CAC. tRF-17 with significantly low expression in breast cancer tissues and serum. The level of tRF-17 differentiated breast cancer from healthy controls with sensitivity of 70.4% and specificity of 68.4%. Overexpression of tRF-17 suppressed cells malignant activity. THBS1 (Thrombospondin-1) as a downstream target of tRF-17, and reduction of THBS1 expression also partially recovered the effects of tRF-17 inhibition on breast cancer cell viability, invasion and migration. Besides, THBS1, TGF-β1, Smad3, p-Smad3 and epithelial-to-mesenchymal transition related genes N-cadherin, MMP3, MMP9 were markedly down-regulated in tRF-17 overexpressing cells. Moreover, tRF-17 attenuated the THBS1-mediated TGF-β1/Smad3 signaling pathway in breast cancer cells. In general, the tRF-17/THBS1/TGF-β1/smad3 axis elucidates the molecular mechanism of breast cancer cells invasion and migration and could lead to a potential therapeutic target for breast cancer.

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CircRNA_101951 promotes migration and invasion of colorectal cancer cells by regulating the KIF3A‑mediated EMT pathway

Cited by 20 publications

References 27 publications

Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer

Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer

circTADA2A Retards the Progression of Colorectal Cancer via Regulating miR-1229/BCL2L10 Signal Axis

tRNA-Derived Fragment tRF-17-79MP9PP Attenuates Cell Invasion and Migration via THBS1/TGF-β1/Smad3 Axis in Breast Cancer

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