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. 2020 Dec 22:13:13097-13109.
doi: 10.2147/OTT.S286627. eCollection 2020.

LncRNA MIR205HG Drives Esophageal Squamous Cell Carcinoma Progression by Regulating miR-214/SOX4 Axis

Hongle Li #  1 , Jinlin Jia #  2 , Lijun Yang  2 , Jie Chu  2 , Jinxiu Sheng  2 , Chang Wang  2 , Weiwei Meng  3 , Zimo Jia  4 , Huiqing Yin  2 , Junhu Wan  2 , Fucheng He  2
Affiliations

LncRNA MIR205HG Drives Esophageal Squamous Cell Carcinoma Progression by Regulating miR-214/SOX4 Axis

Hongle Li et al. Onco Targets Ther. .

Erratum in

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is a common and fatal malignancy, which has posed a great challenge to public health, especially in China. Dysregulation of long non-coding RNAs is involved in the occurrence, development, invasion, and metastasis of multiple cancers including ESCC. However, little is known about the function of MIR205HG in ESCC.

Methods: We used qRT-PCR to detect the expression level of MIR205HG, miR-214, and SOX4 in human ESCC tissues and cell lines. Loss-of-functional assays were performed to test the impact of MIR205HG on cell proliferation, metastasis, and apoptosis process via CCK-8, transwell, and flow cell cytometry assays. Additionally, the downstream molecular mechanism of MIR205HG in ESCC was explored.

Results: Here, we found MIR205HG was substantially up-regulated in ESCC, and there was a positive correlation between MIR205HG expression and tumor size and lymphatic metastasis of ESCC patients. Inhibition of MIR205HG attenuated cell proliferation, migration, and invasion. Silencing MIR205HG increased G1 phase cell counts and decreased S phase cell counts, along with increased apoptotic cell populations. Notably, the rescue assays indicated that miR-214 could partly reverse the influence of MIR205HG on ESCC cell migration. We also found that SOX4 was a direct target mRNA of miR-214, and MIR205HG could act as a molecular sponge to regulate SOX4 expression in ESCC.

Conclusion: Taken together, our findings demonstrate that MIR205HG promotes ESCC progression by regulating the miR-214/SOX4 axis. MIR205HG may be a novel candidate target for ESCC diagnosis and therapy.

Keywords: ESCC; MIR205HG; SOX4; lncRNA; miR-214.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
MIR205HG was significantly elevated in ESCC tissues. (A) The volcano plot showed the differential expression lncRNAs in ESCC tissues. (B) Heatmap analysis showed the top 10 up-regulated lncRNAs in ESCC tissues. (C and D) LINC01468 and LINC01272 were not statistically up-regulated in 45 ESCC tissues. (E) MIR205HG expression abundance was significantly increased in ESCC tissues. (F) The expression of MIR205HG in ESCC from the lnCAR database. ****P<0.0001.
Figure 2
Figure 2
The association between MIR205HG and clinical features of ESCC patients. (A) The results of the ROC analysis of MIR205HG in ESCC. (B) The si-MIR205HG#2 and si-MIR205HG #3 suppressed MIR205HG expression in KYSE30 and EC109 cells. (C) MIR205HG knockdown inhibited KYSE30 cell proliferation. (D) The cell growth rate of the EC109 cell was reduced when silencing of MIR205HG. **P<0.01, ***P<0.001.
Figure 3
Figure 3
MIR205HG increased ESCC cell metastasis. (A–C) The results of the transwell invasion assay in KYSE30 and EC109 cell. (D–F) The results of the transwell migration assay in KYSE30 and EC109 cell. ****P<0.0001.
Figure 4
Figure 4
MIR205HG inhibited ESCC cell apoptosis. (A–D) The number of apoptosis cells was remarkably elevated in the si-MIR205HG group for KYSE30 cells. (E–H) The proportion of apoptosis cells increased in the si-MIR205HG group for EC109 cells. ***P<0.001, ****P<0.0001.
Figure 5
Figure 5
MIR205HG accelerated ESCC cell cycle progression. (A–D) The counts of G1 phase cell was significantly increased in the MIR205HG silence group along with reduced counts of S phase cell according to flow cytometry results. ***P<0.001, ****P<0.0001.
Figure 6
Figure 6
MIR205HG regulated miR-214 expression. (A) The localization of MIR205HG. (B) MIR205HG depletion increased miR-214 expression. (C) MIR205HG expression was negatively related to miR-214 expression in ESCC tissues. (D) The miR −214 inhibitor reduced miR-214 expression in KYSE30 and EC109 cells (control represents the negative control of inhibitor). (E and F) miR-214 partly compromised the migration of MIR205HG in ESCC cells. (G) The binding sites and the result of the dual-luciferase assay of MIR205HG and miR-214. **P<0.01, ***P<0.001, ****P<0.0001.
Figure 7
Figure 7
The high expression of SOX4 in ESCC and the association between SOX4 and MIR205HG. (A) The expression profile of SOX4 in the pan-cancer analysis. (B and C) GEPIA and Oncomine analysis showed SOX4 was significantly elevated in ESCC. (D) The disease-free survival analysis of SOX4 in ESCC. (E) The ROC analysis of SOX4 in ESCC. (F) SOX4 expression was remarkably reduced after knocking down MIR205HG. (G) The miR −214 inhibitor increased SOX4 expression in EC109 cell. (H) The SOX4 protein was reduced after MIR205HG silence in EC109 cell. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.
Figure 8
Figure 8
Mechanistic model of oncogenic function of MIR205HG in ESCC. LncRNA MIR205HG promoted ESCC progression by regulating the miR-214/SOX4 axis.
See this image and copyright information in PMC

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