Table 1.
Oncogenic or tumor suppressive non-coding RNAs with in vivo experimental evidence
| Name | ncRNA | Cancer types examined | In vivo experimental techniques used | Cancer-related mechanisms and/or functions of ncRNA | References |
|---|---|---|---|---|---|
| Oncogenic ncRNAs | |||||
| miR-10b | miRNA | breast, glioblastoma | antimiRs, CRISPR-Cas9 knockdown in mouse xenografts and allografts, transgenic knockout mouse models | targets several transcripts that encode regulators of cell cycle progression, migration, invasion, and metastasis | Ma et al., 2010, Kim et al., 2016, El Fatimy et al., 2017 |
| miR-21 | miRNA | lung, B cell lymphoma | transgenic knockout, overexpression mouse models | targets transcripts that encode negative regulators of RAS signaling, leading to increased proliferation and decreased apoptosis | Hatley et al., 2010, Medina et al., 2010 |
| miR-31 | miRNA | lung, breast | overexpression in mouse xenografts, transgenic knockout, overexpression mouse models | targets transcripts that encode regulators of RAS, WNT, and TGFβ signaling to increase proliferation, stem cell renewal, and metastasis | Edmonds et al., 2016, Lv et al., 2017 |
| miR-155 | miRNA | lymphoma | transgenic overexpression mouse model, treatment with antimiRs | targets SHIP1 transcript, a negative regulator of AKT, to increase proliferation and survival | O’Connell et al., 2009, Babar et al., 2012, Cheng et al., 2015 |
| miR-221 | miRNA | liver | overexpression, treatment with antimiRs in mouse xenografts | targets transcripts of tumor suppressors and cell cycle inhibitors (e.g., p27, PTEN) to increase proliferation and decrease apoptosis | Pineau et al., 2010, Park et al., 2011 |
| LeuCAG3’tsRNA | tsRNA | liver | LNA knockdown in PDX | enhances translation of transcripts encoding ribosomal proteins, leading to increased ribosome biogenesis and proliferation | Kim et al., 2017 |
| ARLNC1 | lncRNA | prostate | shRNA or ASO knockdown in mouse xenografts | interacts with the mRNA encoding AR, a nuclear receptor, to promote oncogenic AR signaling, proliferation, and suraval | Zhang et al., 2018 |
| CamK-A | lncRNA | breast | shRNA, siRNA knockdown in mouse xenografts/PDX | interacts with and controls activity of kinases that modulate calcium-induced NF-KB signaling, leading to remodeling of the tumor microenvironment | Sang et al., 2018 |
| CCAT1 | lncRNA | colorectal, esophageal | shRNA, siRNA knockdown in mouse xenografts | interacts with transcription factors (e.g., SOX2, p63) to activate expression of genes involved in increasing proliferation and decreasing apoptosis | Kim et al., 2014, Jiang et al., 2018 |
| CTBP1-AS | lncRNA | prostate | siRNA knockdown, overexpression in mouse xenografts | recruits chromatin modifying, splicing factors to promoter of a nuclear receptor corepressor (CTBP) to decrease its expression, leading to increased oncogenic AR activity | Takayama et al., 2013 |
| DSCAM-AS1 | lncRNA | breast | shRNA knockdown in mouse xenografts | interacts with proteins of the hnRNP complex involved in RNA processing and mediates proliferation, invasion, and metastasis | Niknafs et al., 2016 |
| EPIC1 | lncRNA | breast | shRNA knockdown in mouse xenografts | interacts with MYC transcription factor and increases its activation of target genes, leading to enhanced cell cycle progression | Wang et al., 2018 |
| FAL1 | lncRNA | ovarian breast | shRNA, siRNA knockdown in mouse xenografts | stabilizes components of PRC1 chromatin modifying complex to mediate expression of genes involved in proliferation and suraval | Hu et al., 2014 |
| HOTAIR | lncRNA | breast | siRNA knockdown, overexpression in mouse xenografts | recruits PRC2, LSD1/CoREST/REST chromatin modifying complexes, scaffolds transcription factors at target promoters of genes involved in invasion, metastasis, and proliferation | Gupta et al., 2010, Li et al., 2016b |
| LINK-A | lncRNA | breast | shRNA knockdown in mouse xenografts, transgenic overexpression in mammary gland, LNA knockdown | interacts with kinases that control HIF1α activity, glycolysis, enhances degradation of tumor suppressors (RB, p53) and antigen peptide-loading complexes to promote immune evasion | Lin et al., 2016, Hu et al., 2019 |
| lncARSR | lncRNA | RCC | shRNA knockdown, overexpression in mouse xenografts | interacts with transcriptional coactivator YAP and acts as a ceRNA for miRNAs that target RTK transcripts, leading to enhanced suraval and propagation of tumor-initiating cells | Qu et al., 2016a, Qu et al., 2016b |
| PCAT-1 | lncRNA | prostate | overexpression in mouse xenografts | represses expression of BRCA2 tumor suppressor to impact DNA damage repair | Prensner et al., 2014a |
| PVT1 | lncRNA | colorectal, gastric | CRISPR-Cas9 or shRNA knockdown, overexpression in mouse xenografts | activates oncogenic signaling (MYC, STAT3) and represses expression of tumor suppressors (p15, p16), resulting in increased proliferation, angiogenesis and decreased apoptosis | Tseng et al., 2014, Kong et al., 2015, Zhao et al., 2018 |
| SAMMSON | lncRNA | melanoma | GapmeR knockdown in PDX | interacts with and controls subcellular localization of proteins that regulate mitochondrial homeostasis and metabolism | Leucci et al., 2016 |
| SChLAP1 | lncRNA | prostate | shRNA knockdown in mouse xenografts | interacts with and antagonizes activity of the SWI/SNF chromatin modifying complex to promote invasion and metastasis | Prensner et al., 2013 |
| THOR | lncRNA | lung, melanoma | CRISPR-Cas9 knockdown, overexpression in mouse xenografts, transgenic knockout, overexpression in zebrafish | binds IGF2BP1 to stabilize interactions with oncogenic target mRNAs, in turn stabilizing those transcripts and promoting proliferation | Hosono et al., 2017 |
| BRAFP1 | pseudogene | B cell lymphoma | transgenic overexpression mouse model | acts as a ceRNA for miRNAs that target the BRAF transcript, leading to increased BRAF expression, MAPK signaling, and proliferation | Karreth et al., 2015 |
| circCCDC66 | circRNA | colorectal | siRNA knockdown in mouse xenografts | sponges several miRNAs that target oncogenic transcripts (e.g., MYC), promoting proliferation, migration, and invasion | Hsiao et al., 2017 |
| circCTNNB1 | circRNA | gastric | shRNA knockdown, overexpression in mouse xenografts | binds a DEAD-box RNA helicase (DDX3) to increase transcription factor (YY1) activation of WNT/p-catenin target genes | Yang et al., 2019 |
| Tumor suppressive ncRNAs | |||||
| let-7 | miRNA | lung | antimiRs, mimetics in mouse xenografts or transgenic lung cancer mouse models | targets several transcripts that encode oncogenes, including RAS, leading to decreased cell cycle progression and proliferation | Trang et al., 2010, Trang et al., 2011 |
| miR-15a/16-1 | miRNA | prostate, leukemia | knockdown, overexpression in mouse xenografts, transgenic knockout mouse | targets several transcripts that encode cyclins, CDKs, and anti-apoptotic proteins, thereby increasing apoptosis and inhibiting proliferation | Bonci et al., 2008, Klein et al., 2010 |
| miR-34a | miRNA | lung, prostate, breast | overexpression, mimetics, antimiRs in mouse xenografts, mimetics in transgenic lung cancer mouse models | targets several oncogenic transcripts encoding cyclins, CDKs, cell adhesion molecules, RTKs, and other non-RTKs, resulting in decreased proliferation, invasion, and suraval | Liu et al., 2011, Trang et al., 2011, Kasinski et al., 2012, Adams et al., 2016b |
| miR-122 | miRNA | liver | transgenic knockout mouse models, overexpression in transgenic liver cancer mouse models | targets expression of several genes involved in lipid metabolism, proliferation, and inflammation | Hsu et al., 2012, Tsai et al., 2012 |
| miR-506 | miRNA | ovanan | mimetics in mouse xenografts | targets SNAI2 transcript to decrease its expression and inhibit migration, invasion, and EMT | Yang et al., 2013a |
| GAS5 | lncRNA | glioblastoma | overexpression in mouse xenografts | acts as a nuclear receptor response element mimic for GR, decreases oncogenic miRNA expression, leading to enhanced apoptosis, decreased proliferation, invasion, and migration | Zhang et al., 2013, Zhao et al., 2015 |
| LET | lncRNA | liver, colorectal | shRNA knockdown, overexpression in mouse xenografts | interacts with and destabilizes a dsRNA binding protein (NF90), a key factor involved in regulation of HIF-1a levels and cell invasion | Yang et al., 2013b |
| MEG3 | lncRNA | lung | overexpression in mouse xenografts | increases p53 tumor suppressor levels to activate apoptosis and decrease proliferation | Lu et al., 2013 |
| PTENP1 | pseudogene | RCC, bladder | overexpression in mouse xenografts | acts as a ceRNA for miRNAs that target the PTEN tumor suppressor transcript, leading to increased apoptosis, decreased proliferation, migration, and invasion | Yu et al., 2014, Zheng et al., 2018 |
| circHIPK3 | circRNA | bladder | overexpression in mouse xenografts | sponges miRNAs to suppress expression of an endoglycosidase (HPSE), thereby decreasing levels of pro-migratory and angiogenic factors | Li et al., 2017 |
| Context-dependent ncRNAs | |||||
| miR-26a | miRNA | glioma, leukemia, liver, colorectal | overexpression in transgenic glioma, liver cancer mouse models, transgenic overexpression mouse models | targets both tumor suppressor (PTEN) and cyclin (CCND2/E2) transcripts to either increase or decrease proliferation, depending on the context | Huse et al., 2009, Kota et al., 2009, Mavrakis et al., 2011, Zeitels et al., 2014 |
| miR-29 | miRNA | leukemia, glioblastoma | mimetics in mouse xenografts, transgenic overexpression mouse models | promotes proliferation in B cells but can also target and decrease expression of transcipts that enhance lipid synthesis (SCAP, SREBP-1), proliferation (CDK6), and apoptosis (MCL-1) | Garzon et al., 2009, Santanam et al., 2010, Ru et al., 2016 |
| MALAT1 | lncRNA | lung, breast | genetic knockout, overexpression in mouse xenografts and allografts, transgenic knockout, overexpression mouse models, ASOs in mouse xenografts or transgenic models | promotes expression of genes involved in metastasis, conversely, shown to also inhibit metastasis through interaction with/inhibition of a pro-metastatic transcription factor (TEAD) | Gutschner et al., 2013, Arun et al., 2016, Kim et al., 2018 |
| NEAT1 | lncRNA | prostate, skin, pancreatic | shRNA knockdown, overexpression in mouse xenografts, transgenic knockout mouse models | mediates oncogenic nuclear receptor (ER) signaling, prevents DNA damage and activation of p53 tumor suppressor, leading to proliferation, invasion, and decreased apoptosis, conversely, shown to also prevent transformation and proliferation in other settings | Chakravarty et al., 2014, Adriaens et al., 2016, Mello et al., 2017 |
| NKILA | lncRNA | breast | shRNA knockdown, overexpression in mouse xenografts/PDX | binds/inhibits NF-KB and downstream inflammation, which increases apoptosis, reduces invasion, promotes activation-induced cell death in CTLs, T>1 cells, leading to immune evasion | Liu et al., 2015, Huang et al., 2018 |
Abbreviations: AR, androgen receptor, ASO, antisense oligonucleotide, CDK, cyclin-dependent kinase, ceRNA, competitive endogenous RNA, circRNA, circular RNA, CTL, cytotoxic T lymphocyte, EMT, epithelial-to-mesenchymal transition, ER, estrogen receptor, GR, glucocorticoid receptor, hnRNP, heterogeneous nuclear ribonucleoprotein, LNA, locked nucleic acid, lncRNA, long non-coding RNA, miRNA, microRNA, ncRNA, non-coding RNA, PDX, patient-derived xenograft, RCC, renal cell carcinoma, RTK, receptor tyrosine kinase, tsRNA, tRNA-derived small RNA