The long intergenic non-coding RNA CCR492 functions as a let-7 competitive endogenous RNA to regulate c-Myc expression

Maldotti, Mara; Incarnato, Danny; Neri, Francesco; Krepelova, Anna; Rapelli, Stefania; Anselmi, Francesca; Parlato, Caterina; Basile, Giulia; Dettori, Daniela; Calogero, Raffaele; Oliviero, Salvatore

doi:10.1016/j.bbagrm.2016.06.010

Cited by 22 publications

(14 citation statements)

References 30 publications

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“…OLR1 is also overexpressed in human cancers and has been found to participate in cancer cell proliferation, apoptosis, migration and angiogenesis [39–41]. Additionally, several lncRNAs (e.g., H19 [42], CCAT1 [43] and CCR492 [44]) have been reported to be ceRNA by sponging let-7 miRNA family in different types of cancer. We observed that LAT2 and OLR1 were upregulated in gemcitabine-resistant pancreatic cell lines and that inhibiting their expression enhanced the chemosensitivity of pancreatic cancer cells to gemcitabine.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA GSTM3TV2 upregulates LAT2 and OLR1 by competitively sponging let-7 to promote gemcitabine resistance in pancreatic cancer

et al. 2019

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Background Chemoresistance is one of the main causes of poor prognosis in pancreatic cancer patients. Understanding the mechanisms implicated in chemoresistance of pancreatic cancer is critical to improving patient outcomes. Recent evidences indicate that the long noncoding RNAs (lncRNAs) are involving in chemoresistance of pancreatic cancer. However, the mechanisms of lncRNAs contribute to resistance in pancreatic cancer and remain largely unknown. The objective of this study is to construct a chemoresistance-related lncRNA-associated competing endogenous RNA (ceRNA) network of pancreatic cancer and identify the key lncRNAs in regulating chemoresistance of the network. Methods Firstly, lncRNA expression profiling of gemcitabine-resistant pancreatic cancer cells was performed to identify lncRNAs related to chemoresistance by microarray analysis. Secondly, with insights into the mechanism of ceRNA, we used a bioinformatics approach to construct a chemoresistance-related lncRNAs-associated ceRNA network. We then identified the topological key lncRNAs in the ceRNA network and demonstrated its function or mechanism in chemoresistance of pancreatic cancer using molecular biological methods. Further studies evaluated its expression to assess its potential association with survival in patients with pancreatic cancer. Results Firstly, we demonstrated that lncRNAs were dysregulated in gemcitabine-resistant pancreatic cancer cells. We then constructed a chemoresistance-related lncRNA-associated ceRNA network and proposed that lncRNA Homo sapiens glutathione S-transferase mu 3, transcript variant 2 and noncoding RNA (GSTM3TV2; NCBI Reference Sequence: NR_024537.1) might act as a key ceRNA to enhance chemoresistance by upregulating L-type amino acid transporter 2 (LAT2) and oxidized low-density lipoprotein receptor 1(OLR1) in pancreatic cancer. Further studies demonstrated that GSTM3TV2, overexpressed in gemcitabine-resistant cells, enhanced the gemcitabine resistance of pancreatic cancer cells in vitro and in vivo. Mechanistically, we identified that GSTM3TV2 upregulated LAT2 and OLR1 by competitively sponging let-7 to promote gemcitabine resistance. In addition, we revealed that the expression levels of GSTM3TV2 were significantly increased in pancreatic cancer tissues and were associated with poor prognosis. Conclusion Our results suggest that GSTM3TV2 is a crucial oncogenic regulator involved in chemoresistance and could be a new therapeutic target or prognostic marker in pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Long noncoding RNA GSTM3TV2 upregulates LAT2 and OLR1 by competitively sponging let-7 to promote gemcitabine resistance in pancreatic cancer

et al. 2019

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“…By sequestering those miRNAs, the following MYC‐induced lncRNAs ensure high MYC levels and create a positive feedback loop on MYC: CCAT1‐S, the short isoform of CCAT1‐L (let‐7a/b/c/e‐5p) (Deng et al ., ), DANCR (miR‐33b‐5p) (Ma et al ., ), H19 (let‐7a/b‐5p) (Peng et al ., ; Zhou et al ., ), linc00176 (miR‐185‐5p) (Tran et al ., ), and SNHG3 (miR‐182a‐5p) (Huang et al ., ). Another lncRNA that ensures high MYC levels by sequestering miRNAs of the let‐7‐5p family without being regulated by MYC is lincRNA CCR492 (Maldotti et al ., ). In contrast, the MYC‐induced lncRNA‐MIF reduces MYC levels and creates a negative feedback loop by sequestering miR‐586 (Zhang et al ., ).…”

Section: Ncrnas Regulating Mycmentioning

confidence: 97%

Intricate crosstalk between MYC and non‐coding RNAs regulates hallmarks of cancer

et al. 2018

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Myelocytomatosis viral oncogene homolog (MYC) plays an important role in the regulation of many cellular processes, and its expression is tightly regulated at the level of transcription, translation, protein stability, and activity. Despite this tight regulation, MYC is overexpressed in many cancers and contributes to multiple hallmarks of cancer. In recent years, it has become clear that noncoding RNAs add a crucial additional layer to the regulation of MYC and its downstream effects. So far, twenty‐five microRNAs and eighteen long noncoding RNAs that regulate MYC have been identified. Thirty‐three miRNAs and nineteen lncRNAs are downstream effectors of MYC that contribute to the broad oncogenic role of MYC, including its effects on diverse hallmarks of cancer. In this review, we give an overview of this extensive, multilayered noncoding RNA network that exists around MYC. Current data clearly show explicit roles of crosstalk between MYC and ncRNAs to allow tumorigenesis.

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“…Long non-coding (lnc) RNA H19, linc - ROR , CCR 492, and lnc RSU1P2 inhibit let - 7 function by acting as sponges. MiR-107 is over-expressed in some breast cancers, linc - ROR in pancreatic ductal adenocarcinoma, and lnc RSU1P2 in cervical cancer, where they contribute to cancer progression and poor prognosis [49, 127–129]. In glioblastoma, insulin-like growth factor 2 binding protein 2 (IMP2) blocks let - 7 function by binding to miRNA recognition elements of let - 7 targets.…”

Section: Let-7 Regulationmentioning

confidence: 99%

Let‐7 as biomarker, prognostic indicator, and therapy for precision medicine in cancer

Chirshev

Oberg

Ioffe

et al. 2019

Clinical & Translational Med

204

183

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Abnormal regulation and expression of microRNAs (miRNAs) has been documented in various diseases including cancer. The miRNA let - 7 (MIRLET7) family controls developmental timing and differentiation. Let - 7 loss contributes to carcinogenesis via an increase in its target oncogenes and stemness factors. Let - 7 targets include genes regulating the cell cycle, cell signaling, and maintenance of differentiation. It is categorized as a tumor suppressor because it reduces cancer aggressiveness, chemoresistance, and radioresistance. However, in rare situations let - 7 acts as an oncogene, increasing cancer migration, invasion, chemoresistance, and expression of genes associated with progression and metastasis. Here, we review let - 7 function as tumor suppressor and oncogene, considering let - 7 as a potential diagnostic and prognostic marker, and a therapeutic target for cancer treatment. We explain the complex regulation and function of different let - 7 family members, pointing to abnormal processes involved in carcinogenesis. Let - 7 is a promising option to complement conventional cancer therapy, but requires a tumor specific delivery method to avoid toxicity. While let - 7 therapy is not yet established, we make the case that assessing its tumor presence is crucial when choosing therapy. Clinical data demonstrate that let - 7 can be used as a biomarker for rational precision medicine decisions, resulting in improved patient survival.

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The long intergenic non-coding RNA CCR492 functions as a let-7 competitive endogenous RNA to regulate c-Myc expression

Cited by 22 publications

References 30 publications

Long noncoding RNA GSTM3TV2 upregulates LAT2 and OLR1 by competitively sponging let-7 to promote gemcitabine resistance in pancreatic cancer

Long noncoding RNA GSTM3TV2 upregulates LAT2 and OLR1 by competitively sponging let-7 to promote gemcitabine resistance in pancreatic cancer

Intricate crosstalk between MYC and non‐coding RNAs regulates hallmarks of cancer

Let‐7 as biomarker, prognostic indicator, and therapy for precision medicine in cancer

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