The Long Noncoding RNA Cancer Susceptibility 9 and RNA Binding Protein Heterogeneous Nuclear Ribonucleoprotein L Form a Complex and Coregulate Genes Linked to AKT Signaling

Klingenberg, Marcel; Groß, Matthias; Goyal, Ashish; Polycarpou‐Schwarz, Maria; Miersch, Thilo; Ernst, Anne-Sophie; Leupold, Jörg Hendrik; Patil, Nagamma; Warnken, Uwe; Allgayer, Heike; Longerich, Thomas; Schirmacher, Peter; Boutros, Michael; Diederichs, Sven

doi:10.1002/hep.30102

Cited by 119 publications

(101 citation statements)

References 48 publications

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“…The authors identified and studied in molecular detail a prominent cytoplasmic lncRNA, CASC9 (cancer susceptibility candidate 9), which was preferentially abundant in HCC compared with normal liver. CASC9 had recently been shown to promote tumorigenesis in the esophagus, stomach, lung, and nasopharynx; in keeping with these findings, CASC9 was also significantly induced in HCCs and correlated inversely with patient survival . Moreover, a series of loss‐of‐function studies revealed that higher expression of CASC9 was strongly associated with major phenotypes observed in liver tumorigenesis, such as excessive proliferation and loss of susceptibility to apoptosis.…”

contrasting

confidence: 58%

“…In this issue of Hepatology, Klingenberg et al (5) report a comprehensive collection of viability-associated lncRNAs in HCC. The authors identified and studied in molecular detail a prominent cytoplasmic lncRNA, CASC9 (cancer susceptibility candidate 9), which was preferentially abundant in HCC compared with normal liver.…”

Section: See Article On Page 1817mentioning

confidence: 99%

“…CASC9 had recently been shown to promote tumorigenesis in the esophagus, stomach, lung, and nasopharynx; in keeping with these findings, CASC9 was also significantly induced in HCCs and correlated inversely with patient survival. (5) Moreover, a series of loss-of-function studies revealed that higher expression of CASC9 was strongly associated with major phenotypes observed in liver tumorigenesis, such as excessive proliferation and loss of susceptibility to apoptosis. However, in contrast to earlier studies reporting that CASC9 was primarily nuclear in other models of carcinogenesis, Klingenberg et al (5) found that CASC9 was largely cytoplasmic in HCC.…”

Section: See Article On Page 1817mentioning

confidence: 99%

“…(5) Moreover, a series of loss-of-function studies revealed that higher expression of CASC9 was strongly associated with major phenotypes observed in liver tumorigenesis, such as excessive proliferation and loss of susceptibility to apoptosis. However, in contrast to earlier studies reporting that CASC9 was primarily nuclear in other models of carcinogenesis, Klingenberg et al (5) found that CASC9 was largely cytoplasmic in HCC. Interestingly, quantitative proteomic analysis using SILAC (stable isotope labeling by amino acids in cell culture) revealed that a major role of CASC9 was to activate the cytoplasmic kinase AKT, as well as the AKT-related network of signaling molecules, including upstream and downstream AKT regulators (e.g., PI3K, mTOR, PTEN, PDK1/2).…”

Section: See Article On Page 1817mentioning

confidence: 99%

“…Thus, interventions to lower CASC9 to inactivate AKT would be expected to dampen cell survival and mitogenic pathways widely and robustly. The impact of CASC9 on HCC cell survival and proliferation was reflected in the broad spectrum of mRNAs and proteins differentially expressed when CASC9 was silenced . The diverse gene expression programs affected by CASC9 abundance likely reflected the fact that the downstream targets of AKT, both direct and indirect, included many transcription factors (e.g., FOXO, NFκB, TP53, HIF1A) and translational regulators (e.g., TSC1/2, mTOR).…”

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confidence: 99%

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AKTions by Cytoplasmic lncRNA CASC9 Promote Hepatocellular Carcinoma Survival

Noh

Gorospe

2018

Hepatology

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contrasting

confidence: 58%

Section: See Article On Page 1817mentioning

confidence: 99%

Section: See Article On Page 1817mentioning

confidence: 99%

Section: See Article On Page 1817mentioning

confidence: 99%

mentioning

confidence: 99%

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AKTions by Cytoplasmic lncRNA CASC9 Promote Hepatocellular Carcinoma Survival

Noh

Gorospe

2018

Hepatology

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Long noncoding RNA LINC01578 drives colon cancer metastasis through a positive feedback loop with the NF‐κB/YY1 axis

et al. 2020

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Metastasis accounts for poor prognosis of cancers and related deaths. Accumulating evidence has shown that long noncoding RNAs (lncRNAs) play critical roles in several types of cancer. However, which lncRNAs contribute to metastasis of colon cancer is still largely unknown. In this study, we found that lncRNA LINC01578 was correlated with metastasis and poor prognosis of colon cancer. LINC01578 was upregulated in colon cancer, associated with metastasis, advanced clinical stages, poor overall survival, disease-specific survival, and disease-free survival. Gain-of-function and loss-of-function assays revealed that LINC01578 enhanced colon cancer cell viability and mobility in vitro and colon cancer liver metastasis in vivo. Mechanistically, nuclear factor kappa B (NF-jB) and Yin Yang 1 (YY1) directly bound to the LINC01578 promoter, enhanced its activity, and activated LINC01578 expression. LINC01578 was shown to be a chromatin-bound lncRNA, which directly bound NFKBIB promoter. Furthermore, LINC01578 interacted with and recruited EZH2 to NFKBIB promoter and further repressed NFKBIB expression, thereby activating NF-jB signaling. Through activation of NF-jB, LINC01578 further upregulated YY1 expression. Through activation of the NF-jB/YY1 axis, LINC01578 in turn enhanced its own promoter activity, suggesting that LINC01578 and NF-jB/YY1 formed a positive feedback loop. Blocking NF-jB signaling abolished the oncogenic roles of LINC01578 in colon cancer. Furthermore, the expression levels of LINC01578, NFKBIB, and YY1 were correlated in clinical tissues. Collectively, this study demonstrated that LINC01578 promoted colon cancer metastasis via forming a positive feedback loop with NF-jB/YY1 and suggested that LINC01578 represents a potential prognostic biomarker and therapeutic target for colon cancer metastasis.

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New insights into the interplay between long non‐coding RNAs and RNA‐binding proteins in cancer

Yao

Yang

Sun

et al. 2022

Cancer Communications

140

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With the development of proteomics and epigenetics, a large number of RNAbinding proteins (RBPs) have been discovered in recent years, and the interaction between long non-coding RNAs (lncRNAs) and RBPs has also received increasing attention. It is extremely important to conduct in-depth research on the lncRNA-RBP interaction network, especially in the context of its role in the occurrence and development of cancer. Increasing evidence has demonstrated that lncRNA-RBP interactions play a vital role in cancer progression; therefore, targeting these interactions could provide new insights for cancer drug discovery. In this review, we discussed how lncRNAs can interact with RBPs to regulate their localization, modification, stability, and activity and discussed the effects of RBPs on the stability, transport, transcription, and localization of lncRNAs. Moreover, we explored the regulation and influence of these interactions on lncRNAs, RBPs, and downstream pathways that are related to cancer development, such as N6-methyladenosine (m6A) modification of lncRNAs.In addition, we discussed how the lncRNA-RBP interaction network regulates cancer cell phenotypes, such as proliferation, apoptosis, metastasis, drug resistance, immunity, tumor environment, and metabolism. Furthermore, we summarized the therapeutic strategies that target the lncRNA-RBP interaction network. Although these treatments are still in the experimental stage and various theories and processes are still being studied, we believe that these strategies may provide new ideas for cancer treatment.

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The Long Noncoding RNA Cancer Susceptibility 9 and RNA Binding Protein Heterogeneous Nuclear Ribonucleoprotein L Form a Complex and Coregulate Genes Linked to AKT Signaling

Cited by 119 publications

References 48 publications

AKTions by Cytoplasmic lncRNA CASC9 Promote Hepatocellular Carcinoma Survival

AKTions by Cytoplasmic lncRNA CASC9 Promote Hepatocellular Carcinoma Survival

Long noncoding RNA LINC01578 drives colon cancer metastasis through a positive feedback loop with the NF‐κB/YY1 axis

New insights into the interplay between long non‐coding RNAs and RNA‐binding proteins in cancer

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