# LncRNA SNHG11 facilitates tumor metastasis by interacting with and stabilizing HIF-1α

**Authors:** Linguo Xu, Lin Huan, Tianan Guo, Yangjun Wu, Yanfang Liu, Qifeng Wang, Shenglin Huang, Ye Xu, Linhui Liang, Xianghuo He

PMC · DOI: 10.1038/s41388-020-01512-8 · Oncogene · 2020-10-15

## TL;DR

The lncRNA SNHG11 promotes colorectal cancer metastasis by stabilizing HIF-1α, a protein linked to tumor growth under low oxygen conditions.

## Contribution

This study reveals a novel mechanism where SNHG11 interacts with and stabilizes HIF-1α, promoting tumor metastasis in CRC.

## Key findings

- SNHG11 is upregulated by promoter hypomethylation in CRC and is linked to poor patient prognosis.
- SNHG11 promotes CRC cell migration and metastasis under hypoxia by stabilizing HIF-1α.
- SNHG11 binds to HIF-1α, blocking its degradation and upregulating HIF-1α target genes like AK4, ENO1, HK2, and Twist1.

## Abstract

Epigenetic alteration is one of the hallmarks of colorectal cancer (CRC). Many driver genes are regulated by DNA methylation in CRC. However, the role of DNA methylation regulating lncRNAs remain elusive. Here, we identify that SNHG11 (small nucleolar RNA host gene 11) is upregulated by promotor hypomethylation in CRC and is associated with poor prognosis in CRC patients. SNHG11 can promote CRC cell migration and metastasis under hypoxia. Interestingly, the DNA-binding motif of SNHG11 is similar to that of HIF-1α. In addition, SNHG11-associated genes are enriched with members of the HIF-1 signaling pathway in CRC. Mechanistically, SNHG11 binds to the pVHLrecognition sites on HIF-1α, thus blocking the interaction of pVHL with HIF-1α and preventing its ubiquitination and degradation. Moreover, SNHG11 upregulates the expression of HIF-1α target genes, i.e., AK4, ENO1, HK2, and Twist1. Notably, SNHG11 can bind to the HRE sites in the promoter of these genes and increase their transcription. In summary, these results identify a SNHG11/ HIF-1α axis that plays a pivotal role in tumor invasion and metastasis.

## Linked entities

- **Genes:** SNHG11 (small nucleolar RNA host gene 11) [NCBI Gene 128439], AK4 (adenylate kinase 4) [NCBI Gene 205], ENO1 (enolase 1) [NCBI Gene 2023], HK2 (hexokinase 2) [NCBI Gene 3099], TWIST1 (twist family bHLH transcription factor 1) [NCBI Gene 7291]
- **Proteins:** HIF1A (hypoxia inducible factor 1 subunit alpha), VHL (von Hippel-Lindau tumor suppressor)
- **Diseases:** colorectal cancer (MONDO:0005575)

## Full-text entities

- **Genes:** POTEF (POTE ankyrin domain family member F) [NCBI Gene 728378] {aka A26C1B, POTE2alpha, POTEACTIN}, MIR429 (microRNA 429) [NCBI Gene 554210] {aka MIRN429, hsa-mir-429, mir-429}, ENO1 (enolase 1) [NCBI Gene 2023] {aka ENO1-IT1, ENO1L1, HEL-S-17, MPB1, NNE, PPH}, PTK6 (protein tyrosine kinase 6) [NCBI Gene 5753] {aka BRK}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, HK2 (hexokinase 2) [NCBI Gene 3099] {aka HKII, HXK2}, TP53COR1 (tumor protein p53 pathway corepressor 1) [NCBI Gene 102800311] {aka TRP53COR1, linc-p21, lincRNA-p21}, Snhg11 (small nucleolar RNA host gene 11) [NCBI Gene 319317] {aka A930034L06Rik, E130013N09Rik}, VHL (von Hippel-Lindau tumor suppressor) [NCBI Gene 7428] {aka HRCA1, RCA1, VHL1, pVHL}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, CTCF (CCCTC-binding factor) [NCBI Gene 10664] {aka CFAP108, FAP108, MRD21}, YY1 (YY1 transcription factor) [NCBI Gene 7528] {aka DELTA, GADEVS, INO80S, NF-E1, UCRBP, YIN-YANG-1}, MIR200B (microRNA 200b) [NCBI Gene 406984] {aka MIRN200B, mir-200b}, AK4 (adenylate kinase 4) [NCBI Gene 205] {aka AK 4, AK3, AK3L1, AK3L2}, MIR200C (microRNA 200c) [NCBI Gene 406985] {aka MIRN200C, mir-200c}, PVT1 (Pvt1 oncogene) [NCBI Gene 5820] {aka LINC00079, MIR1204HG, NCRNA00079, TP53LC09, onco-lncRNA-100}, POLR2A (RNA polymerase II subunit A) [NCBI Gene 5430] {aka NEDHIB, POLR2, POLRA, RPB1, RPBh1, RPO2}, EGLN1 (egl-9 family hypoxia inducible factor 1) [NCBI Gene 54583] {aka C1orf12, ECYT3, HALAH, HIF-PH2, HIFPH2, HPH-2}, TWIST1 (twist family bHLH transcription factor 1) [NCBI Gene 7291] {aka ACS3, BPES2, BPES3, CRS, CRS1, CSO}, MIR31HG (MIR31 host gene) [NCBI Gene 554202] {aka LncHIFCAR, hsa-lnc-31}, GPNMB (glycoprotein nmb) [NCBI Gene 10457] {aka HGFIN, NMB, PLCA3}, SNHG11 (small nucleolar RNA host gene 11) [NCBI Gene 128439] {aka C20orf198, LINC00101, NCRNA00101}
- **Diseases:** pulmonary nodules (MESH:D055613), SCID (MESH:D053632), invasion (MESH:D009361), kidney renal clear cell carcinoma (MESH:D002292), prostate adenocarcinoma (MESH:D000230), metastasis (MESH:D009362), Cancer (MESH:D009369), oral cancer (MESH:D009062), NOD (MESH:D020191), breast invasive carcinoma (MESH:D001943), hypoxic (MESH:D002534), COAD (MESH:D029424), CRC (MESH:D015179), hypoxia (MESH:D000860), infection (MESH:D007239), rectum adenocarcinoma (MESH:D012004), lymphatic invasion (MESH:D008207),  (MESH:D018450)
- **Species:** Homo sapiens (human, species) [taxon 9606], Lentivirus (genus) [taxon 11646], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** HEK293T — Homo sapiens (Human), Transformed cell line (CVCL_0063), U2 — Homo sapiens (Human), Fibrosarcoma, Cancer cell line (CVCL_M019), HTC-116 — Rattus norvegicus (Rat), Rat hepatocellular carcinoma, Cancer cell line (CVCL_3382), HCT-116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), RKO — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0504), LoVo — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0399)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC7661343/full.md

## References

39 references — full list in the complete paper: https://tomesphere.com/paper/PMC7661343/full.md

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Source: https://tomesphere.com/paper/PMC7661343