Collective evidence has indicated that lncRNA SNHG20 is closely related to cancer. Initially, lncRNA SNHG20 was identified as an overexpressed oncogene in hepatocellular carcinoma[11]. Its overexpression is associated with tumor size, clinical stage, and poor prognosis in patients with hepatocellular carcinoma. Currently, lncRNA SNHG20 has been confirmed as a dysregulated oncogene in other several malignancies, such as gastric cancer [11], glioblastoma [17], NSCLC [18]. Moreover, the silence of SNHG20 significantly suppressed cell proliferation, migration, and invasion in a variety of human cancers. It has drawn great attention as carcinogenic lncRNA in many kinds of cancers. Many researchers focused on the clinical potential value in predicting cancer prognosis. However, inconsistency regarding the predictive value of lncRNA SNHG20 in some prognostic parameters, e.g., TNM stage, LNM, and DM, arise from a wide range of studies due to heterogeneity.
In the present meta-analysis, we found that patients with elevated SNHG20 expression tended to have poorer OS in cancer patients. Namely, high lncRNA SNHG20 expression may serve as an independent predictive factor for the prognosis of cancer patients. Meanwhile, this study also revealed that SNHG20 overexpression significantly associated with more advanced TNM stage, higher risk of LNM and DM. To sum up, our finding suggested that lncRNA could serve as a potential independent prognostic factor for predicting clinical outcomes for cancer patients. However, the underlying molecular mechanism of aberrant SNHG20 expression correlated with poor clinical prognosis remains elusive.
Many studies have investigated the functional mechanism of lncRNA SNHG20 on tumorigenesis and tumor progression in various cancers (Table 2). Previous studies have reported that SNHG20 could provide specific functional scaffolds for regulatory complexes, such as EZH2. SNHG20 acted/function as an oncogene to interact with EZH2 to inhibit the expression of E-cadherin and p21 in the GC and NSCLC cells [12, 28]. Wnt/β-catenin signal pathway has been revealed to be involved in the regulation of cell proliferation, migration, and invasion in certain cancers [29, 30]. It was reported that lncRNA SNHG20 could promote the proliferation, migration, and invasion of bladder cancer and ovarian cancer by activating the Wnt/β-catenin signal pathway[27, 31]. Moreover, several important pathway was confirmed to be modulated by SNHG20 in various cancers, including GSK-3β/β-catenin signaling pathway in gastric cancer [28], MDM2-p53 pathway and PTEN/PI3K/AKT signaling pathway in glioma [32, 33], PI3K/Akt/mTOR signaling pathway in glioblastoma [17], ATM-JAK-PD-L1 pathway in ESCC [25], and MEK/ERK pathway in cervical cancer [34]. Furthermore, SNHG20 could promote vasculogenic mimicry formation of glioma cells by activating FOXK1 [35] and accelerate the proliferation of hepatocellular carcinoma by upregulate HBx and downregulate PTEN [36].
Table 2
Molecular mechanism of SNHG20 in cancer initiation and progression.
Cancer type | Molecular Mechanism | Functions | References |
GC | Downregulate miR-140-5p to increase NDRG3;downregulate miR-295-3p to inhibit ZFX,inhibit p21 to regulate GSK-3β/β-catenin signaling pathway | promote cell proliferation to mediate resistance to 5-FU in gastric cancer, prognostic biomarker and associated with tumor size and lymphatic metastasis, promote epithelial-mesenchymal transition (EMT) | [15][28][37] |
Glioma | Sponge miR-4486 to regulate the MDM2-p53 pathway;increase POXK1;activate PTEN/PI3K/AKT signaling pathway | promote cell proliferation, migration, decrease the apoptosis percentage;promote vasculogenic mimicry formation of glioma cells | [32][33][35] |
LSCC | Suppress miR-140 expression | Promote cell proliferation, prognostic biomarker and correlated with tumor stage. | [21] |
Glioblastoma | Activate PI3K/Akt/mTOR signaling pathway | Promote cell proliferation, decrease cell apoptosis and remain stem properties | [17] |
EOC | NA | Prognostic biomarker and correlated with histological grade and lymph node status, promote cell proliferation, migration, and invasion | [13] |
NSCLC | Suppress miR-154 and elevating ZEB2 and RUNX2 expression,repress P21 | Promote cell proliferation, migration, invasion and decrease apoptosis. Prognostic biomarker and correlate with advanced tumor, lymph node and metastases (TNM) stage and tumor size | [12][18] |
ESCC | Modulate ATM-JAK-PD-L1 pathway | Promote cell proliferation, migration, invasion, EMT, and decrease apoptosis.Prognostic biomarker and correlate with tumor size, lymph node metastasis, TNM stage, and tumor grade | [25] |
HCC | Upregulate HBx and downregulate PTEN, increase ZEB1, ZEB2, N-cadherin and Vimentin expression and down-regulated E-cadherin | Promote proliferation,invasion and decrease apoptosis, prognostic biomarker and correlate with tumor size and advanced TNM stage | [11][22][36] |
OSCC | Downregulate miR-197 to increase LIN28 | Prognostic biomarker and associate with tumor differentiation and Tumor-Node-Metastasis stage,promote proliferation. | [16][38] |
Osteosarcoma | Downregulate miR-139 to increase RUNX2 | Prognostic biomarker and associate with Enneking stage, distant metastasis, and histological grade, Promote proliferation, invasion and decrease apoptosis | [24][26] |
Bladder cancer | Activate the Wnt/β-catenin signalling pathway | Prognostic biomarker and associate with advanced clinical stage, lymph node metastasis | [27] |
Cervical cancer | Downregulate miR-140-5p to increase ADAM10 and inhibit MEK/ERK pathway | Promote proliferation and invasion | [34] |
Breast cancer | Downregulate miR-495 to increase HER2 | Promote proliferation, invasion, and migration | [39] |
Ovarian cancer | Activate the Wnt/β-catenin signalling pathway | Promote ovarian cancer progression | [31] |
Colorectal cancer | NA | Prognostic biomarker and associate with advanced TNM stage | [19] |
NC | Upregulate TGF-β1 | Prognostic biomarker and associate with distant tumor metastasis. | [23] |
Notes:GC: gastric cancer; LSCC: laryngeal squamous cell carcinoma; EOC: epithelial ovarian cancer;NSCLC: non-small cell lung cancer; ESCC: esophageal squamous cell carcinoma; HCC: hepatocellular carcinoma; OSCC: oral squamous cell carcinoma; NC: nasopharyngeal carcinoma |
In addition, growing evidence has demonstrated that SNHG20 function as competitive endogenous RNA (ceRNA) to regulate miRNAs, and plays a key role in the initiation, development, and chemoresistance of cancer. In gastric cancer, Yu et al. demonstrated that SNHG20 contribute to 5-fluorouracil resistance through SNHG20/miR-140-5p/NDRG3 regulatory pathway, providing a brand new insight for the 5-fluorouracil resistance of gastric cancer [37]. Recently, miR-295-3p was found to be a target of SNHG20 in gastric cancer by Cui et al. [15]. In cervical cancer, Guo et al. also demonstrated that SNHG20 could function as an oncogenic lncRNA by regulating miR-140-5p/ADAM10 axis [34]. Furthermore, SNHG20 function as a ceRNA to promote malignant progression of human cancers through competitive sponging of miR-4486 in glioma [32], miR-140 in LSCC [21], miR-154 in NSCLC [18], miR-197 in OSCC [38], miR-139 in osteosarcoma [24], and miR-495 in breast cancer [39].
Several limitations existed in this meta-analysis owing to the discrete data across these clinical studies. First, all included studies were performed in China, which might limit the applicability of our results for other ethnic population. Second, the cut-off values are different among the included articles. Third, some of the HRs were calculated by reconstructing survival curves, which might result in a calculation bias. Finally, only studies published in English or Chinese were obtained in this meta-analysis, and the data collection may be incomplete.