Long non-coding RNA CASC9 promotes tumor growth and metastasis via modulating FZD6/Wnt/β-catenin signaling pathway in bladder cancer

Zhan, Yonghao; Zhang, Lianghao; Yu, Shuanbao; Wen, Jianguo; Liu, Yuchen; Zhang, Xuepei

doi:10.1186/s13046-020-01624-9

Cited by 34 publications

(32 citation statements)

References 39 publications

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“…The functional assays after RAMS11 downregulation displayed signi cantly reduced CRC cell survival, proliferation, and migration. Our results are in line with previous studies that demonstrated knockdown or knockout of lncRNAs, such as H19, SNHG14, CCAL, and MIR17HG (31)(32)(33)(34)(35), potentially reduced CRC cell proliferation, migration, metastasis, and increased chemo-sensitivity.…”

Section: Discussionsupporting

confidence: 93%

RAMS11 promotes CRC through mTOR-dependent inhibition of autophagy, suppression of apoptosis, and promotion of epithelial-mesenchymal transition

Khan

Law

2021

Preprint

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Background Long non-coding RNAs (lncRNAs), a class of non-coding RNAs (ncRNAs) associated with diverse biological processes of cells. Over the past decades, cumulating research evidences revealed that abnormal expressions of lncRNAs are associated with colorectal cancer (CRC) initiation, progression, metastasis, and resistance to therapies. Moreover, their usefulness as candidate biomarkers for CRC diagnosis and prognosis are well evident throughout previous literature. In the current study, we examined the role and molecular mechanisms of newly identified lncRNA named RNA associated with metastasis-11 (RAMS11) in CRC development. Methods The expression of RAMS11 in CRC cell lines DLD-1, HT-29, HCT-116, and SW480 and colon normal cells CCD-112-CoN were evaluated by quantitative RT-qPCR. The results showed that the RAMS11 is significantly upregulated in CRC cell lines compared to the normal cells. The CCK-8 proliferation assay, colony formation assay, and migration assay were performed to evaluate the biological and physiological functions of RAMS11 in vitro . To decipher the molecular mechanisms of RAMS11 medicated CRC progression, we further performed western blot analysis of the key pathway proteins (e.g., AMPK, AKT, and mTOR). Results Our results revealed that higher expression of RAMS11 is associated with increased CRC proliferation, migration, and development of metastasis. Knockdown of RAMS11 induced autophagy, apoptosis along with reduction of epithelial-mesenchymal transition (EMT) suggesting that RAMS11 is involved in CRC progression. The molecular mechanisms of RAMS11 indicated that knockdown of RAMS11 significantly inhibited CRC carcinogenesis through mTOR-dependent autophagy induction. Conclusions In sum, our results suggested that RAMS11 is an important oncogene in CRC pathogenesis. Targeting RAMS11 could be a potential therapeutic strategy for CRC management.

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Section: Discussionsupporting

confidence: 93%

RAMS11 promotes CRC through mTOR-dependent inhibition of autophagy, suppression of apoptosis, and promotion of epithelial-mesenchymal transition

Khan

Law

2021

Preprint

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“…Mechanistically, SOX2OT upregulates SOX2 expression by sponging miR-200c 10 . In addition, many lncRNAs such as CASC9 42 , SNHG1 43 , TUG1 44 , and NBAT1 45 are associated with the occurrence and development of bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

Hypomethylation of PlncRNA-1 promoter enhances bladder cancer progression through the miR-136-5p/Smad3 axis

et al. 2020

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Apart from being potential prognostic biomarkers and therapeutic targets, long non-coding RNAs (lncRNAs) modulate the development and progression of multiple cancers. PlncRNA-1 is a newly discovered lncRNA that exhibits the above properties through multiple regulatory pathways. However, the clinical significance and molecular mechanisms of PlncRNA-1 in bladder cancer have not been established. PlncRNA-1 was found to be overexpressed in 71.43% of bladder cancer tissues. Moreover, the expression level correlated with tumor invasion, T stage, age, and number of tumors, but not with gender, recurrent status, preoperative treatment, pathological grade, and tumor size. The expression level of PlncRNA-1 can, to a certain extent, be used as a predictor of the degree of tumor invasion and T stage among BC patients. Inhibiting PlncRNA-1 expression impaired the proliferation, migration, and invasion of T24 and 5637 bladder cancer cells in vitro and in vivo. Specifically, PlncRNA-1 promoter in BC tissues was found to be hypomethylated at position 131 (36157603 on chromosome 21). PlncRNA-1 promoter hypomethylation induces the overexpression of PlncRNA-1. In addition, PlncRNA-1 modulated the expression of smad3 and has-miR-136-5p (miR-136). Conversely, miR-136 regulated the expression of PlncRNA-1 and smad3. PlncRNA-1 mimics competitive endogenous RNA (ceRNA) in its regulation of smad3 expression by binding miR-136. Rescue analysis further revealed that modulation of miR-136 could reverse the expression of smad3 and epithelial–mesenchymal transition (EMT) marker proteins impaired by PlncRNA-1. In summary, PlncRNA-1 has important clinical predictive values and is involved in the post-transcriptional regulation of smad3. The PlncRNA-1/miR-136/smad3 axis provides insights into the regulatory mechanism of BC, thus may serve as a potential therapeutic target and prognostic biomarker for cancer.

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“…28 In bladder cancer, lncRNA CASC9 acted as a miR-497-5p sponge to up-regulate the expression of FZD6, activate theWnt/β-cateninsignaling pathway, as well as promote the growth and metastasis of bladder cancer. 29 Additional studies have revealed that circFGFR3 participates in the miR-29a-3p/E2F1 axis by inducing the EMT process of ovarian cancer cells and promote the initiation of ovarian cancer. 30 In total, we found 113 DEmRNAs in the established ceRNA network.…”

Section: Discussionmentioning

confidence: 99%

<p>Identification of a Functional ceRNA Network to Explore Potential Biomarkers for Hepatocellular Carcinoma</p>

Zao

Liu

Liang

et al. 2020

OTT

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To establish a novel circRNA-miRNA-mRNA network associated with the poor prognosis of hepatocellular carcinoma (HCC). Materials and Methods: Quantitative real-time PCR was used to verify the differentially expressed circRNA. Moreover, the competing endogenous RNA networks were established using bioinformatics methods. Meanwhile, the prognostic value and potential mechanism of ceRNA network in hepatocellular carcinoma (HCC) were analyzed. Results: This work found that circ_0130911 was highly expressed in HCC tissues and early recurring HCC. Further, we effectively constructed a ceRNA network. The ceRNA network regulated by circ_0130911 might influence the prognosis of HCC by regulating cell cyclerelated pathways. Conclusion: The ceRNA network proposed here can be used as a novel biomarker for the prognosis of HCC, thereby providing new insights for the targeted therapy of HCC.

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Long non-coding RNA CASC9 promotes tumor growth and metastasis via modulating FZD6/Wnt/β-catenin signaling pathway in bladder cancer

Cited by 34 publications

References 39 publications

RAMS11 promotes CRC through mTOR-dependent inhibition of autophagy, suppression of apoptosis, and promotion of epithelial-mesenchymal transition

RAMS11 promotes CRC through mTOR-dependent inhibition of autophagy, suppression of apoptosis, and promotion of epithelial-mesenchymal transition

Hypomethylation of PlncRNA-1 promoter enhances bladder cancer progression through the miR-136-5p/Smad3 axis

<p>Identification of a Functional ceRNA Network to Explore Potential Biomarkers for Hepatocellular Carcinoma</p>

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