SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop

Bian, Zehua; Zhou, Mingyue; Cui, Kaisa; Yang, Fan; Cao, Yulin; Sun, Shengbai; Liu, Bingxin; Gong, Liang; Li, Jiuming; Wang, Xue; Li, Chaoqun; Yao, Surui; Yin, Yuan; Huang, Shenglin; Fei, Bojian; Huang, Zhaohui

doi:10.1186/s13046-021-02162-8

SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop

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Published: 15 November 2021

Volume 40, article number 360, (2021)
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SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop

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Zehua Bian¹^na1,
Mingyue Zhou¹^na1,
Kaisa Cui¹,
Fan Yang¹,
Yulin Cao¹,
Shengbai Sun¹,
Bingxin Liu¹,
Liang Gong²,
Jiuming Li²,
Xue Wang²,
Chaoqun Li¹,
Surui Yao¹,
Yuan Yin¹,
Shenglin Huang³,
Bojian Fei⁴ &
…
Zhaohui Huang ORCID: orcid.org/0000-0002-0117-9976^1,2

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Abstract

Background

Small nucleolar RNA host gene (SNHG) long noncoding RNAs (lncRNAs) are frequently dysregulated in human cancers and involved in tumorigenesis and progression. SNHG17 has been reported as a candidate oncogene in several cancer types, however, its regulatory role in colorectal cancer (CRC) is unclear.

Methods

SNHG17 expression in multiple CRC cohorts was assessed by RT-qPCR or bioinformatic analyses. Cell viability was evaluated using Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell mobility and invasiveness were assessed by Transwell assays. Tumor xenograft and metastasis models were applied to confirm the effects of SNHG17 on CRC tumorigenesis and metastasis in vivo. Immunohistochemistry staining was used to measure protein expression in cancer tissues. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase assays were used to investigate the molecular mechanism of SNHG17 in CRC.

Results

Using multiple cohorts, we confirmed that SNHG17 is aberrantly upregulated in CRC and correlated with poor survival. In vitro and in vivo functional assays indicated that SNHG17 facilitates CRC proliferation and metastasis. SNHG17 impedes PES1 degradation by inhibiting Trim23-mediated ubiquitination of PES1. SNHG17 upregulates FOSL2 by sponging miR-339-5p, and FOSL2 transcription activates SNHG17 expression, uncovering a SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop.

Conclusions

We identified SNHG17 as an oncogenic lncRNA in CRC and identified abnormal upregulation of SNHG17 as a prognostic risk factor for CRC. Our mechanistic investigations demonstrated, for the first time, that SNHG17 promotes tumor growth and metastasis through two different regulatory mechanisms, SNHG17-Trim23-PES1 axis and SNHG17-miR-339-5p-FOSL2-SNHG17 positive feedback loop, which may be exploited for CRC therapy.

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Background

Colorectal cancer (CRC) is the third most prevalent malignant tumor and one of the leading causes of cancer-related death worldwide [1]. Despite progress in surgery, chemotherapy and radiotherapy, the prognosis of CRC is still poor due to its postoperative recurrence and metastasis. Therefore, it is urgent to explore the molecular mechanism of CRC and to develop new therapeutic targets.

Long noncoding RNAs (lncRNAs) are a class of transcribed RNAs with lengths greater than 200 nucleotides, and their protein coding ability is lost or restricted [2]. Recent studies have shown that lncRNAs play vital roles in regulating various biological processes, such as proliferation, differentiation, apoptosis, and chemoresistance [3]. Growing evidence has shown that the abnormal regulation or expression of lncRNAs is implicated in the tumorigenesis and progression of CRC [4, 5]. We have reported that some lncRNAs regulate CRC growth, metastasis and chemoresistance and may be potential prognostic biomarkers or therapeutic targets [6,7,8,9,10,11,12]. Recently, other groups also reported the regulatory roles of some lncRNAs, including ENO1-IT1 [13], LINC00460 [14], RAMS11 [15] and FLANC [16], in CRC development and progression. All these studies indicate the key regulatory roles of lncRNAs in CRC.

Small nucleolar RNAs (snoRNAs) are predominantly distributed in the nucleolus and play a role in guiding the sequence-specific chemical modification or processing of pre-ribosomal RNA [17]. As the host genes of snoRNAs, lncRNA small nucleolar RNA host genes (SNHGs) have been shown to be abnormally expressed in multiple cancers and regulate cell proliferation, metastasis, and chemoresistance [18, Full size image

To identify which region of SNHG17 binds to PES1, we constructed a series of SNHG17 deletion mutants based on the predicted secondary structure of SNHG17 in the AnnoLnc2 database (http://annolnc.gao-lab.org/index.php). RNA fragments were transcribed in vitro from these deletion mutant constructs and used for RNA pull-down assays. Western blotting analyses of PES1 in protein samples pulled down by these different SNHG17 constructs showed that RNA fragments with the 1–500 deletion nearly completely lost their ability to bind PES1, suggesting that the N-terminus of SNHG17 is essential for the binding of SNHG17 to PES1 (Fig. 3c). To further investigate which domain of PES1 accounts for its interaction with SNHG17, we performed RIP assays using a series of HA-tagged PES1 deletion mutants. As shown in Fig. 3d, the BRCT domain of PES1 is essential for the binding of PES1 to SNHG17 (Fig. 3d).

SNHG17 blocks PES1 ubiquitination and degradation

Given that SNHG17 interacts with the PES1 in CRC cells, we next investigated the molecular consequence of this association on PES1 expression. The results showed that the protein levels of PES1 were significantly increased in SNHG17-overexpressing HCT116 cells and decreased in SNHG17-silenced LoVo cells (Fig. 3e), whereas no obvious effect was observed on the mRNA levels of PES1 (Supplementary Fig. 5). These results suggest that SNHG17 can increase PES1 protein expression at the posttranscriptional level. To further validate this observation, we used the protein synthesis inhibitor cycloheximide (CHX) to evaluate the effect of SNHG17 on the protein stability of PES1. SNHG17 markedly increased the half-life of PES1 in HCT116 cells, whereas silencing SNHG17 expression reduced the half-life of PES1 degradation in LoVo cells (Fig. 3f). Moreover, treatment with the proteasome inhibitor MG132 attenuated the accumulation of endogenous PES1 in SNHG17-overexpressing cells and the reduction in PES1 expression in SNHG17 knockdown CRC cells (Fig. 3 g). These data suggest that SNHG17 interferes with PES1 degradation through the ubiquitin-proteasome system. Furthermore, the ubiquitination levels of PES1 significantly decreased in SNHG17-overexpressing cells (Fig. 3 h).

A recent study revealed that Trim23 is an E3 ligase for PES1 ubiquitination and degradation [26]. To investigate whether SNHG17 inhibits the effect of Trim23 on the degradation of PES1, we co-transfected SNHG17 and Trim23 expression vectors into CRC cells, and showed that Trim23 overexpression could decrease PES protein level, while SNHG17 overexpression could restore the decreased PES1 protein level caused by Trim23 overexpression (Fig. 3i). Next, we examined the effect of SNHG17 on the interaction between Trim23 and PES1 in CRC cells using IP assays. Indeed, SNHG17 knockdown notably increased this association in CRC cells, suggesting that SNHG17 increases the protein stability of PES1 by inhibiting Trim23-mediated ubiquitination of PES1 (Fig. 3j). We have confirmed that the BRCT domain of PES1 is crucial for the binding of PES1 to SNHG17 (Fig. 3d), which suggests that SNHG17 can compete with Trim23 to bind the BRCT domain of PES1, thereby inhibits Trim23-mediated ubiquitination and degradation of PES1. Therefore, we performed IP assays using a series of HA-tagged PES1 deletion mutants. As shown in Fig. 3 k, the BRCT domain of PES1 is also essential for the binding of PES1 to Trim23. Together, these results demonstrate that SNHG17 increases the protein levels of PES1 by binding PES1 and then inhibiting Trim23-mediated ubiquitination and degradation of PES1.

SNHG17 binds with miR-339-5p

Numerous studies have demonstrated that cytoplasmic lncRNAs post-transcriptionally regulate downstream genes by binding with microRNAs (miRNAs). We detected the subcellular localization of SNHG17 using RT-qPCR and FISH assays and demonstrated that SNHG17 was located in both the cytoplasm and nucleus of HCT116 and LoVo cells (Fig. 4a and Supplementary Fig. 6). We predicted miRNAs that could regulate SNHG17 using StarBase and RegRNA 2.0 tools and identified six candidate miRNAs (miR-339-5p, − 1913, − 3619-5p, − 3180-3p, − 3909, and − 5581-3p) (Fig. 4b). Subsequently, we confirmed that miR-339-5p and miR-3909 could bind to SNHG17 through luciferase assays, and miR-339-5p had the strongest inhibitory effect on SNHG17 (Fig. 4c). We also showed that miR-339-5p was significantly downregulated in CRC tissues from the TCGA CRC and GEO GSE30454 datasets (Supplementary Fig. 7). Therefore, miR-339-5p was chosen for further studies. We constructed luciferase reporter vectors of SNHG17 segments containing WT or MUT miR-339-5p binding sites. Luciferase reporter assays revealed that miR-339-5p significantly decreased the reporter activity of the SNHG17-WT plasmid, whereas no obvious changes were observed in the mutant group, indicating that SNHG17 could specifically interact with miR-339-5p (Fig. 4d). Furthermore, the RIP assay showed that both SNHG17 and miR-339-5p were enriched in Ago2-containing miRNA ribonucleoprotein complexes (miRNPs) (Fig. 4e).

FOSL2 is a functional target of SNHG17/miR-339-5p axis

Next, to identify the downstream target of the SNHG17/miR-339-5p axis, we analyzed the mRNA targets of the SNHG17-ceRNA network predicted by StarBase and the target genes of miR-339-5p predicted by TargetScan and identified that FOSL2 is a potential downstream target of the SNHG17/miR-339-5p axis in CRC (Fig. 4f). To further verify our speculation, we performed luciferase reporter assays in 293 T and HCT116 cells and showed that miR-339-5p significantly inhibited the reporter activity of the FOSL2 WT 3′ untranslated region (UTR) group but not that of the MUT group (Fig. 4 g). To further evaluate the relationships among SNHG17, miR-339-5p and FOSL2, pluc-FOSL2–3′ UTR-WT plasmids were cotransfected with miR-339-5p and SNHG17 into CRC cells for a luciferase assay, and the results indicated that ectopic SNHG17 expression could block the downregulation of luciferase activity induced by miR-339-5p (Fig. 4 h). Moreover, both the RNA and protein expression levels of FOSL2 were significantly increased in SNHG17-overexpressing HCT116 cells and decreased in SNHG17-depleted LoVo cells compared with their corresponding control cells (Fig. 4i). In addition, we revealed that the miR-339-5p inhibitor could increase the expression of FOSL2 compared with that in the control group, whereas ectopic miR-339-5p expression in CRC cells significantly decreased the expression of FOSL2 (Fig. 4j). Additional rescue assays confirmed that ectopic FOSL2 expression partly restored the cell proliferation and migration activities, which were decreased by miR-339-5p in CRC cells (Fig. 4 k-m). Moreover, SNHG17 overexpression partly restored the expression of the FOSL2 target genes (MYC, SNAI2 and SOX4) impaired by FOSL2 knockdown in HCT116 cells (Fig. 4n). All these results suggest that FOSL2 is a direct functional target of the SNHG17/miR-339-5p axis in CRC cells.

SNHG17 overexpression is driven by FOSL2

The mechanism mediating SNHG17 overexpression in CRC remains unclear. We scanned the binding sites of transcription factors on the regulatory element of SNHG17 by employing the JASPAR database. Interestingly, we observed several FOSL2 binding sites at the promoter of SNHG17, suggesting direct regulation of SNHG17 by FOSL2 (Fig. 5a). To validate our hypothesis, we knocked down the expression of FOSL2 in CRC cells with siRNAs and found that inhibiting FOSL2 expression significantly decreased the expression of SNHG17 (Fig. 5b and c). We then performed a luciferase assay to investigate whether FOSL2 directly regulates the transcription of SNHG17. We searched for the canonical binding site of FOSL2 predicted by JASPAR in the promoter region of SNHG17, and the three sites with the highest scores were selected for experimental verification. After mutating all three potential binding sites, luciferase assays suggested that the second binding site is the key site mediating the transcriptional regulation of SNHG17 by FOSL2 (Fig. 5d). To further substantiate this, we carried out additional luciferase reporter assays in FOSL2-depleted CRC cells. The results showed that FOSL2 knockdown reduced the activity of the WT SNHG17 promoter, which was abolished when site 2 was mutated (Fig. 5e). Moreover, ChIP assays confirmed the interaction between FOSL2 and putative binding site 2 in the SNHG17 promoter (Fig. 5f). We also examined the mRNA levels of FOSL2 in CRC tissues and revealed the upregulation of FOSL2 in CRC (Fig. 5 g). Moreover, Pearson correlation analysis showed that the expression of FOSL2 was positively correlated with that of SNHG17 in CRC tissues (Fig. 5 h, r = 0.4024, P = 0.0005). Together, these data demonstrate that FOSL2 directly drives SNHG17 overexpression in CRC by transcriptional activation.

PES1 and FOSL2 are upregulated in CRC and positively correlated with SNHG17 expression

To further confirm the relationships among SNHG17 and PES1 and FOSL2, the protein expression of PES1 and FOSL2 in CRC tissues was assessed using IHC. The results indicated that tumor tissues showed increased PES1 and FOSL2 expression compared with NCTs (Fig. 6a). Survival analyses revealed that high protein expression of PES1 or FOSL2 was closely related to poor survival (log rank = 5.446, P = 0.0196, Fig. 6b) (log rank = 5.657, P = 0.0174, Fig. 6c). Moreover, the protein expression of both PES1 and FOSL2 in human CRC tissues was positively correlated with the expression of SNHG17 (Fig. 6d and e). Meanwhile, the positive relationship between SNHG17 and PES1 (or FOSL2) levels was also observed in CRC xenografts in nude mice (Supplementary Fig. 8). The prognosis of CRC patients with high expression of SNHG17 and PES1 (FOSL2) was significantly worse than that of other CRC patients (log rank = 9.410, P = 0.0022, Fig. 6f) (log rank = 6.933, P = 0.0085, Fig. 6 g). We further showed that the protein levels of PES1 were positively correlated with those of FOSL2 in CRC tissues (r = 0.3256, P = 0.0002, Fig. 6 h), and high expression of both PES1 and FOSL2 in CRC tissues indicated a poor prognosis in CRC patients (log rank = 10.09, P = 0.0015, Fig. 6i). In summary, these data suggest that PES1 and FOSL2 are candidate downstream targets of SNHG17.

SNHG17 plays a carcinogenic role in CRC through PES1 and FOSL2

To investigate whether SNHG17 regulates CRC development and progression through PES1 and FOSL2, we designed rescue assays. It was confirmed that both PES1 and FOSL2 could inhibit cell proliferation in CRC cells, whereas the impact of SNHG17 on CRC cell proliferation was abolished by PES1 or FOSL2 knockdown (Fig. 7a-d). PES1 or FOSL2 knockdown also partly blocked the effects of SNHG17 overexpression on the migration of CRC cells (Fig. 7e and f). Collectively, we found that SNHG17 exerts tumor-promoting functions through PES1 and FOSL2 (Fig. 7 g).

Discussion

CRC is one of the most common malignant tumors of the digestive system. LncRNAs can act as oncogenes or tumor suppressors, and their dysregulation is highly associated with the development and progression of CRC. SNHG17 was initially confirmed to be highly expressed in CRC, and then its overexpression was observed in a variety of cancers. Recent studies have indicated the oncogenic role of SNHG17 in several cancer types, including CRC. For example, recent studies showed that SNHG17 promotes tumor cell proliferation and invasion in tongue squamous cell carcinoma and CRC by sponging miR-23a-3p and miR-876, respectively [25, 27]. In addition, SNHG17 aggravates prostate cancer progression by positively regulating its homolog SNORA71B [28]. All these data suggest that SNHG17 is a pan-cancer oncogene and may be a promising therapeutic target across cancers.

In this study, we confirmed that SNHG17 is significantly upregulated in CRC tissues and was associated with poor survival in multiple CRC cohorts. Functionally, SNHG17 can promote CRC proliferation and metastasis. SNHG17 exerts tumor-promoting functions by two different mechanisms. We demonstrated that PES1 is a SNHG17-associated protein. PES1 is highly evolutionarily conserved and is involved in ribosome biogenesis and cell proliferation [29]. The ribosome is an important organ that is responsible for protein synthesis. To meet the needs for the continuous growth of tumor cells, it is necessary to increase ribosome biogenesis to maintain high protein synthesis efficiency. Therefore, increased ribosome biogenesis is an important feature of cancer cells [30]. Wang et al. reported that PES1 promotes tumorigenesis in hepatocellular carcinoma by regulating the PI3K/AKT pathway [31]. It has been reported that PES1 interacts with BRD4 to enhance c-Myc expression, thereby promoting cell growth and cell resistance to extra-terminal inhibitors in pancreatic cancer [32]. In addition, a recent study revealed that PES1 facilitates telomerase assembly and negatively correlates with senescence in cancer cells, suggesting that PES1 is a promising target for cancer therapy [33]. All these data suggest that PES1 plays an oncogenic role in various cancers. In this study, we showed that SNHG17 binds to PES1 and increases its protein expression in CRC cells. Mechanistically, SNHG17 interacts with PES1 to inhibit the Trim23-mediated ubiquitination of PES1, resulting in increased PES1 stability and enhanced tumor growth and metastasis. Clinical analyses revealed that PES1 is significantly upregulated in CRC tissues and predicts a poor prognosis. These findings suggest that targeting the SNHG17-PES1 regulatory axis is a promising strategy for CRC treatment.

SNHG17 is mainly located in cytoplasm. Most cytoplasmic lncRNAs act as miRNA sponges and are involved in miRNA-mediated posttranscriptional regulation. SNHG17 has already been confirmed to facilitate cell growth by modulating the miR-384/ELF1 axis in oral squamous cell carcinoma [34]. SNHG17 can promote tumor-like behavior in hepatocellular carcinoma cells via miR-3180-3p/RFX1 [35]. These results suggest that binding with miRNAs is one of the most important mechanisms of SNHG17 in cancer. In addition to the SNHG17-Trim23-PES1 mechanism, we also verified that SNHG17 could bind with miR-339-5p and inhibit its function. Previous studies have demonstrated that exosome-derived miR-339-5p mediates radiosensitivity by inhibiting Cdc25A [36]. MiR-339-5p has also been reported to inhibit glycolysis and colon cancer growth by reducing PKM2 expression through hnRNPA1 and PTBP1 [37]. In addition, we confirmed the tumor-suppressive effect of miR-339-5p in CRC and found that it was inhibited by SNHG17.

We further searched for the targets of SNHG17/miR-339-5p and revealed that FOSL2 is a novel functional target of miR-339-5p. Subsequent functional experiments confirmed that SNHG17 regulates CRC development and progression by competitively sponging miR-339-5p and restoring the activity of FOSL2. FOSL2 and the oncoproteins Fos and Jun belongs to the activator protein 1 transcription factor family that transactivates the transcription of its downstream targets. Aberrantly increased expression of FOSL2 has been documented in many cancer types, including CRC. Previous studies have shown that FOSL2 promotes the proliferation, migration, and invasion of various cancers, including non-small-cell lung cancer [38], hepatocellular carcinoma [39], and CRC [40]. We also observed that FOSL2 is upregulated and positively correlates with SNHG17 expression in CRC tissues, which is positively associated with and predicts poor clinical outcomes. Interestingly, we identified a putative binding site of FOSL2 at the promoter of SNHG17 and uncovered that FOSL2 transcriptionally activates SNHG17 expression by binding to this site. Collectively, our data revealed a positive feedback loop of SNHG17-miR-339-5p-FOSL2-SNHG17 in CRC and suggest that targeting this loop might be a promising strategy for CRC therapy.

Conclusion

Overall, our study uncovered two different molecular mechanisms by which SNHG17 promotes CRC development and progression. SNHG17, miR-339-5p, PES1, FOSL2 and their downstream targets form a complicated regulatory network that contributes to colorectal tumorigenesis and metastasis. These data may inspire the development of conceptually novel cancer therapeutics.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

CRC:: Colorectal cancer
LncRNAs:: Long noncoding RNAs;
SNHG:: Small nucleolar RNA host gene
CCK-8:: Cell Counting Kit-8
ATCC:: American Type Culture Collection
RT-qPCR:: Quantitative reverse transcription PCR
FISH:: Fluorescence in situ hybridization
RIP:: RNA immunoprecipitation
ChIP:: Chromatin immunoprecipitation
IHC:: Immunohistochemistry
TCGA:: The Cancer Genome Atlas
GEO:: Gene Expression Omnibus
CCLE:: Cancer Cell Line Encyclopedia
miRNAs:: microRNAs

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Acknowledgements

Not applicable.

Funding

This study was partially supported by grants from the National Natural Science Foundation of China (81802469, 81972220 and 82173063), Top Talent Support Program for young and middle-aged people of Wuxi Health Committee (HB2020044), Project of Wuxi Health Committee (Z201806 and Z202005), Social Development Project of Jiangsu Province (BE2019632), Medical Key Professionals Program of Jiangsu Province (AF052141 and LGY2019017), Wuxi Medical Innovation Team (CXTP003), Wuxi Taihu Lake Talent Plan, China Postdoctoral Science Foundation (2020 M681493), Postdoctoral Science Foundation of Jiangsu Province (2020Z050).

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Zehua Bian and Mingyue Zhou contributed equally to this work.

Authors and Affiliations

Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, 214062, Jiangsu, China
Zehua Bian, Mingyue Zhou, Kaisa Cui, Fan Yang, Yulin Cao, Shengbai Sun, Bingxin Liu, Chaoqun Li, Surui Yao, Yuan Yin & Zhaohui Huang
Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, China
Liang Gong, Jiuming Li, Xue Wang & Zhaohui Huang
Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
Shenglin Huang
Department of Surgical Oncology, Affiliated Hospital of Jiangnan University, 200 Hui He Road, Wuxi, 214062, Jiangsu, China
Bojian Fei

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Zehua Bian
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Mingyue Zhou
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Kaisa Cui
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Fan Yang
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Yulin Cao
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Shengbai Sun
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Bingxin Liu
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Liang Gong
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Jiuming Li
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Xue Wang
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Chaoqun Li
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Surui Yao
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Yuan Yin
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Shenglin Huang
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Bojian Fei
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Zhaohui Huang
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Contributions

BZ, FB, and HZ conceived and designed the project. BZ, ZM, CK, YF, CY, SS, LB, GL, and LJ performed experiments and/ or data acquisition and analyses. WX, LC, YS, YY, HS, and FB provided animals, acquired and managed patients, provided technical, or material support. BZ, ZM, and HZ prepared, wrote, and/or revised the paper. The author(s) read and approved the final manuscript.

Corresponding authors

Correspondence to Bojian Fei or Zhaohui Huang.

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Ethics approval and consent to participate

The present study was approved by the Clinical Research Ethics Committees of the participating institutions. All in vivo animal experiments were approved by the Committee on the Ethics of Animal Experiments of Jiangnan University.

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Not applicable.

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The authors declare that they have no competing interests.

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Additional file 1.

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Bian, Z., Zhou, M., Cui, K. et al. SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop. J Exp Clin Cancer Res 40, 360 (2021). https://doi.org/10.1186/s13046-021-02162-8

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Received: 05 July 2021
Accepted: 30 October 2021
Published: 15 November 2021
DOI: https://doi.org/10.1186/s13046-021-02162-8

SNHG17 promotes colorectal tumorigenesis and metastasis via regulating Trim23-PES1 axis and miR-339-5p-FOSL2-SNHG17 positive feedback loop

Abstract

Background

Methods

Results

Conclusions

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The long noncoding RNA SNHG1 regulates colorectal cancer cell growth through interactions with EZH2 and miR-154-5p

Background

SNHG17 blocks PES1 ubiquitination and degradation

SNHG17 binds with miR-339-5p

FOSL2 is a functional target of SNHG17/miR-339-5p axis

SNHG17 overexpression is driven by FOSL2

PES1 and FOSL2 are upregulated in CRC and positively correlated with SNHG17 expression

SNHG17 plays a carcinogenic role in CRC through PES1 and FOSL2

Discussion

Conclusion

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Additional file 1.

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