Mechanisms of long non‐coding RNA function in colorectal cancer tumorigenesis

Poursheikhani, Arash; Abbaszadegan, Mohammad Reza; Kerachian, Mohammad Amin

doi:10.1111/ajco.13452

Cited by 36 publications

(25 citation statements)

References 196 publications

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“…In the last decade, considerable studies have identified that lncRNAs played critical roles in carcinogenesis and metastasis (Lv et al 2021 ; Yao et al 2019 ; Poursheikhani et al 2021 ). To data, the ceRNA hypothesis sparked new areas of lncRNA research on gene expression regulation, but some controversy still surrounded it (Tay et al 2011 ; Smillie et al 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Association of CASC18/miR-20a-3p/TGFB2 ceRNA axis with occult lymph node metastasis in tongue squamous cell carcinoma

Zhou

Liu

et al. 2021

Mol Med

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Background Tongue squamous cell carcinoma (TSCC) ranks as the most prevalent malignancy in the oral cavity. TSCC patients with occult lymph node metastasis (OLNM) are thought to be at risk of worse outcome. However, regulatory mechanisms underlying OLNM remain less investigated. Methods In the present study, CASC18/miR-20a-3p/TGFB2 axis was identified and evaluated by bioinformatic and qRT-PCR analyses. Effects of CASC18 knockdown on cell migration and invasion were determined by wound healing and transwell assays. Western blot, ELISA, RNA pulldown and luciferase reporter assays were performed for mechanism verification. Results CASC18 was identified up-regulating in TSCC tumours, and especially in those from patients with OLNM. Importantly, we found higher CASC18 expression was positively correlated with the presence of OLNM and worse outcome of TSCC patients. Furthermore, we demonstrated that CASC18 knockdown repressed cell migration and invasion through inhibiting epithelial-mesenchymal transition, which could be partly rescued by miR-20a-3p inhibitor. Regarding the molecular mechanism, we further confirmed that CASC18 functioned as a ceRNA to sponge miR-20a-3p to enhanceTGFB2 expression and secretion. Conclusion In conclusion, we have reported a novel CASC18/miR-20a-3p/TGFB2 ceRNA axis in OLNM of TSCC. Our findings will contribute to a deeper understanding of the molecular mechanism of OLNM in TSCC, and facilitate the development of diagnostic methods for assisting treatment decision-making.

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Section: Discussionmentioning

confidence: 99%

Association of CASC18/miR-20a-3p/TGFB2 ceRNA axis with occult lymph node metastasis in tongue squamous cell carcinoma

Zhou

Liu

et al. 2021

Mol Med

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“…LncRNAs can regulate gene expression, mainly at the post-transcriptional level, via various modes of direct action or as miRNA sponges or endogenous competitors, thus reducing their regulatory effect on target mRNAs [66]. The aberrant expression of lncRNAs, exemplified by lncRNA H19 and lncRNA 91H, an antisense gene of H19, has been implicated in the tumorigenesis and metastasis of different types of cancer, including CRC, where it is associated with a poor prognosis and a high risk of tumor metastasis [67,68]. Both LINC01354 and lncRNA CASC11 are upregulated in CRC and contribute to the pro-liferation, invasion, and metastasis of CRC via activation of the Wnt/β-catenin signaling pathway [69,70].…”

Section: Discussionmentioning

confidence: 99%

“…Several genetic variants located in lncRNA genes influence the risk of CRC development; polymorphisms in lncRNA HOTTIP, rs145204276 and rs55829688 in lncRNA GAS5, rs2839698 in lncRNA H19, rs2632159 in lncRNA PCAT1, rs2147578 in lnc-LAMC2-1:1, and rs664589 in MALAT1 were associated with a significantly increased CRC risk [67], while rs13252298 and rs1456315 in lncRNA PRNCR1 and rs1194338 in MALAT1 had protective effects on CRC [67,74]. It has been suggested that the rs664589 G allele alters the binding of MALAT1 to miR-194-5p, resulting in an increased expression of MALAT1 and enhanced CRC development and metastasis [75], while the rs2147578 in lnc-LAMC2-1:1 affects the sponging of miR-128-3p, which correlates with higher expression of the LAMC2 oncogene in CRC [76].…”

Section: Discussionmentioning

confidence: 99%

GWAS Links New Variant in Long Non-Coding RNA LINC02006 with Colorectal Cancer Susceptibility

Hennig

Kluska

Piątkowska

et al. 2021

Biology

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Despite great efforts, most of the genetic factors contributing to the risk of colorectal cancer (CRC) remain undetermined. Including small but homogenous populations in genome-wide association studies (GWAS) can help us discover new common risk variants specific to the studied population. In this study, including 465 CRC patients and 1548 controls, a pooled DNA samples-based GWAS was conducted in search of genetic variants associated with CRC in a Polish population. Combined with a new method of selecting single-nucleotide polymorphisms (SNPs) for verification in individual DNA samples, this approach allowed the detection of five new susceptibility loci not previously reported for CRC. The discovered loci were found to explain 10% of the overall risk of developing CRC. The strongest association was observed for rs10935945 in long non-coding RNA LINC02006 (3q25.2). Three other SNPs were also located within genes (rs17575184 in NEGR1, rs11060839 in PIWIL1, rs12935896 in BCAS3), while one was intergenic (rs9927668 at 16p13.2). An expression quantitative trait locus (eQTL) bioinformatic analysis suggested that these polymorphisms may affect transcription factor binding sites. In conclusion, four of the identified variants were located within genes likely involved in tumor invasiveness and metastasis. Therefore, they could possibly be markers of poor prognosis in CRC patients.

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“…LncRNAs are a group of non-coding RNAs with more than 200 nt in length and with no or little capability of coding proteins [ 14 – 16 ]. They have been demonstrated to play different canonical roles in diverse biological processes such as cell proliferation, differentiation, and cellular development, carcinogenesis, and metastasis through regulating cornerstone genes expression [ 4 , 17 ]. Numerous investigations highlighted the crucial role of lncRNAs in cancer development and progression [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA AC087388.1 as a novel biomarker in colorectal cancer

2022

Self Cite

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Background Several investigations have reported diverse roles of long non-coding RNA (lncRNA) in biological processes, tumor development, and progression of colorectal cancer (CRC). In this study, we investigated the lncRNA AC087388.1 tumorigenic role in CRC cells. Methods The CRC tissues were collected at the Reza Radiotherapy and Oncology Center, Mashhad, Iran. The human SW-48 and HT-29 CRC cell lines were obtained from the national cell bank of Iran. The cells were cultured according to ATCC (the American Type Culture Collection) recommendations. Quantitative real-time PCR was applied to assess the RNA expression. ShRNA transfection was done to downregulate the target gene. MTT and apoptosis assays were conducted to evaluate cell proliferation and viability, respectively. Colony formation assay, wound healing assay, and invasion assay were applied to determine growth, motility, and invasion of the cells, respectively. ENCORI online tool was used as downstream enrichment analysis. Results Forty CRC patients were encompassed in this study. The results demonstrated that the lncRNA SLC16A1-AS1, AC087388.1, and ELFN1-AS1 were significantly overexpressed in the CRC tissues in comparison to their normal counterpart margins. All the lncRNAs have shown significant Area Under Curve (AUC) values in the patients. Downregulation of lncRNA AC087388.1 remarkably decreased the cell proliferation and viability of the CRC cells. In addition, the data demonstrated that the downregulation of lncRNA AC087388.1 significantly suppressed cell growth and colony formation capability in the cells. Also, downregulation of lncRNA AC087388.1 attenuated motility and invasion of CRC cells, and significantly decreased the expression of invasion genes. In-silico functional enrichment analysis indicated that the lncRNA AC087388.1 has contributed to crucial signaling pathways in tumorigenesis such as the p53 and Wnt signaling pathways, apoptosis, and cell cycle. Conclusions Altogether, we showed that lncRNA AC087388.1 has an oncogenic role in tumorigenesis of CRC, and it can be considered as a novel diagnostic and prognostic biomarker in CRC.

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Mechanisms of long non‐coding RNA function in colorectal cancer tumorigenesis

Cited by 36 publications

References 196 publications

Association of CASC18/miR-20a-3p/TGFB2 ceRNA axis with occult lymph node metastasis in tongue squamous cell carcinoma

Association of CASC18/miR-20a-3p/TGFB2 ceRNA axis with occult lymph node metastasis in tongue squamous cell carcinoma

GWAS Links New Variant in Long Non-Coding RNA LINC02006 with Colorectal Cancer Susceptibility

Long non-coding RNA AC087388.1 as a novel biomarker in colorectal cancer

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