The role of noncoding RNAs in epithelial cancer

Agostini, Massimiliano; Ganini, Carlo; Candi, Eleonora; Melino, Gerry

doi:10.1038/s41420-020-0247-6

Cited by 38 publications

(28 citation statements)

References 150 publications

(152 reference statements)

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“…lncRNAs have received increasing attention in the past decade due to their important roles in human cancer types ( 32 , 33 ). Numerous lncRNAs, such as ubiquitin conjugating enzyme E2 R2-AS1 ( 34 ), colorectal neoplasia differentially expressed ( 35 ) and snail family transcriptional repressor 3-AS1 ( 36 ), are differentially expressed in HCC and are closely associated with clinicopathological factors and prognosis of patients with HCC ( 37 – 39 ).…”

Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA MKLN1‑AS aggravates hepatocellular carcinoma progression by functioning as a molecular sponge for miR‑654‑3p, thereby promoting hepatoma‑derived growth factor expression

Gao¹,

Chen²,

Chi³

et al. 2020

Int J Mol Med

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Long non-coding RNAs (lncRNAs) have recently gained attention due to their important roles in human cancer types, such as breast and gastric cancer. The present study measured alterations in muskelin 1 antisense RNA (MKLN1-AS) expression in hepatocellular carcinoma (Hcc) and evaluated its clinical value in patients with Hcc. Additionally, the current study investigated the effects of MKLN1-AS on the malignant features of Hcc cells. The detailed molecular mechanisms underlying the cancer-promoting activities of MKLN1-AS in Hcc cells were also elucidated. MKLN1-AS expression in Hcc tissues and cell lines was detected using reverse-transcription quantitative PCR (RT-qPCR). Cell Counting Kit-8 assays and flow cytometry were used to determine the roles of MKLN1-AS in Hcc cell proliferation and apoptosis. Migration and invasion assays, as well as tumor xenograft experiments were conducted to analyze migration and invasion in vitro and tumor growth in vivo, respectively. The interaction among microRNA-654-3p (miR-654-3p), MKLN1-AS and hepatoma-derived growth factor (HdGF) in Hcc was investigated using luciferase reporter assay, RNA immunoprecipitation assay, RT-qPcR, western blotting and rescue experiments. MKLN1-AS was upregulated in Hcc tissues and cell lines, and a high MKLN1-AS expression was associated with shorter overall survival and disease-free survival in patients with Hcc. Functionally, the knockdown of MKLN1-AS impaired Hcc cell proliferation, migration and invasion, as well as induced cell apoptosis in vitro. Knockdown of MKLN1-AS expression also inhibited cell proliferation in vivo. The results indicated that MKLN1-AS functioned as a competing endogenous RNA by sponging miR-654-3p in Hcc cells. Additionally, miR-654-3p targeting of HdGF was positively modulated by MKLN1-AS, and miR-654-3p knockdown partially abrogated this effect. Rescue experiments demonstrated that knockdown of miR-654-3p and overexpression of HdGF both abolished MKLN1-AS knockdown-induced cellular processes in Hcc. In summary, MKLN1-AS induced pro-oncogenic effects during Hcc progression by serving as a molecular sponge for miR-654-3p to increase HdGF expression. Therefore, the MKLN1-AS/miR-654-3p/HdGF axis may offer a novel target for the diagnosis, prognosis, prevention and treatment of Hcc.

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Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA MKLN1‑AS aggravates hepatocellular carcinoma progression by functioning as a molecular sponge for miR‑654‑3p, thereby promoting hepatoma‑derived growth factor expression

Gao¹,

Chen²,

Chi³

et al. 2020

Int J Mol Med

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“…Over the last few years, lncRNAs have received considerable attention because of their important roles in human cancers. [40][41][42] An increasing number of studies have reported that several lncRNAs are differentially expressed in CRC and contribute to colorectal carcinogenesis and cancer. [43][44][45] LncRNAs promote or suppress diverse malignant processes in CRC, playing oncogenic or tumor-suppressing roles.…”

Section: Discussionmentioning

confidence: 99%

<p>Long Non-Coding RNA C1QTNF1 Antisense RNA 1 Upregulates Hexokinase 2 by Sponging microRNA-484 to Promote the Malignancy of Colorectal Cancer</p>

Jin¹,

Liu²,

Wang³

et al. 2020

CMAR

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The long noncoding RNA C1QTNF1 antisense RNA 1 (C1QTNF1-AS1) contributes to hepatocellular carcinoma development. However, its expression and roles in colorectal cancer (CRC) have not been fully explored. Therefore, this study determined the expression and roles of C1QTNF1-AS1 in CRC and elucidated its detailed mechanism of action. Methods: C1QTNF1-AS1 expression in CRC tissues and cell lines was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We used Cell Counting Kit-8, flow cytometry, cell migration and invasion assays, and a xenograft tumor model to test the effects of C1QTNF1-AS1 on CRC malignancy. The associations among C1QTNF1-AS1, microRNA-484 (miR-484), and hexokinase 2 (HK2) were explored using luciferase reporter assay, RNA immunoprecipitation, RT-qPCR, and Western blotting. Results: C1QTNF1-AS1 was overexpressed in CRC and related to poor prognosis. C1QTNF1-AS1 interference inhibited CRC cell proliferation, migration, and invasion but induced apoptosis. Furthermore, C1QTNF1-AS1 deficiency impaired tumor growth in vivo. Mechanistically, C1QTNF1-AS1 adsorbed miR-484, thereby increasing the expression of its target HK2. Rescue experiments revealed that the effects of C1QTNF1-AS1 deficiency in CRC cells were reversed by inhibiting miR-484 or upregulating HK2. Conclusion: C1QTNF1-AS1 drives CRC progression by sponging miR-484 and consequently upregulating HK2. The C1QTNF1-AS1/miR-484/HK2 pathway may serve as a diagnostic and therapeutic target for CRC.

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“…Results from this study revealed that oncomiR genes were favorably located in amplified regions, in contrast to tumor-suppressive miRNA genes that tended to be localized to deleted regions. Similar studies have allowed researchers to identify hundreds of novel miRNAs in many cancer types [ 81 , 82 , 83 , 84 ]. Further, it is well established that in order for primary tumor cells to metastasize to distant organs, tumor cells must interact with the surrounding microenvironment.…”

Section: Roles Of Exosomal Micrornas In Breast Cancer Metastasismentioning

confidence: 99%

Exosomal MicroRNAs and Organotropism in Breast Cancer Metastasis

Wong

Jalboush

2020

Cancers

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Breast cancer is the most frequent malignancy for women in which one in eight women will be diagnosed with the disease in their lifetime. Despite advances made in treating primary breast cancer, there is still no effective treatment for metastatic breast cancer. Consequently, metastatic breast cancer is responsible for 90% of breast cancer-related deaths while only accounting for approximately one third of all breast cancer cases. To help develop effective treatments for metastatic breast cancer, it is important to gain a deeper understanding of the mechanisms by which breast cancer metastasizes, particularly, those underlying organotropism towards brain, bone, and lungs. In this review, we will primarily focus on the roles that circulating exosomal microRNAs (miRNAs) play in organotropism of breast cancer metastasis. Exosomes are extracellular vesicles that play critical roles in intercellular communication. MicroRNAs can be encapsulated in exosomes; cargo-loaded exosomes can be secreted by tumor cells into the tumor microenvironment to facilitate tumor–stroma interactions or released to circulation to prime distant organs for subsequent metastasis. Here, we will summarize our current knowledge on the biogenesis of exosomes and miRNAs, mechanisms of cargo sorting into exosomes, the exosomal miRNAs implicated in breast cancer metastasis, and therapeutic exosomal miRNAs.

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The role of noncoding RNAs in epithelial cancer

Cited by 38 publications

References 150 publications

Long non‑coding RNA MKLN1‑AS aggravates hepatocellular carcinoma progression by functioning as a molecular sponge for miR‑654‑3p, thereby promoting hepatoma‑derived growth factor expression

Long non‑coding RNA MKLN1‑AS aggravates hepatocellular carcinoma progression by functioning as a molecular sponge for miR‑654‑3p, thereby promoting hepatoma‑derived growth factor expression

<p>Long Non-Coding RNA C1QTNF1 Antisense RNA 1 Upregulates Hexokinase 2 by Sponging microRNA-484 to Promote the Malignancy of Colorectal Cancer</p>

Exosomal MicroRNAs and Organotropism in Breast Cancer Metastasis

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