Decreased expression of the long non-coding RNA <i>HOXD-AS2</i> promotes gastric cancer progression by targeting HOXD8 and activating PI3K/Akt signaling pathway

Lin, Yu; Ye, Peng-Cheng; Tan, Wanlong; Luo, Yang; Xiang, Wanping; Liu, Zilin; Fu, Zhiming; Lu, Fei; Tang, Lixia; Xiao, Jiangwei

doi:10.4251/wjgo.v12.i11.1237

Cited by 14 publications

(11 citation statements)

References 29 publications

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“…Initially, it was found that lncRNA HOXD-AS2 could regulate the A172 cell cycle to promote glioma progression [ 9 ]. However, a recent study has shown that decreased expression of the long noncoding RNA HOXD-AS2 promotes gastric cancer progression by targeting HOXD8 , which activates the PI3K/Akt signaling pathway [ 10 ]. In our previous study with microarrays of glioma specimens, we found that HOXD-AS2 was aberrantly expressed in glioma [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of lncRNA HOXD-AS2 Improves the Prognosis of Glioma Patients by Inhibiting the Proliferation and Migration of Glioma Cells

Chen

Zhao

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Increasing studies reported that long noncoding RNAs are involved in regulating glioma progression. However, the specific roles and mechanisms of lncRNAs in glioma remain unclear. Here, we sought to explore the functions of HOXD-AS2 in glioma progression. Methods. Gene expressions of lncRNAs in 5 normal brain tissue specimens and 5 glioblastoma tissue specimens were detected by gene expression profile chip technology. Bioinformatic analysis was performed to see whether differential expression of lncRNAs played any significant role in glioma occurrence and progression. The relationship between HOXD-AS2 level and clinical prognosis of the patients was analyzed. HOXD-AS2 was specifically interfered with by siRNA technology to observe its effects on U251 cell growth, proliferation, apoptosis, and invasion. Results. The expression level of HOXD-AS2 gene in glioma was significantly higher than that in the normal brain tissue, which was related to the tumor grade. The level of HOXD-AS2 gene in patients with high-grade glioma was higher than that in patients with low-grade glioma. High expression of HOXD-AS2 gene was a risk factor for poor prognosis of glioma patients. Knocking down the expression of HOXD-AS2 in glioma cell line U251 arrested the cell cycle and reduced the cell proliferation. Furthermore, it could significantly reduce the migration ability of the cells but had no significant effect on the invasion. Conclusion. HOXD-AS2 is an oncogenic lncRNA associated with the poor prognosis of glioma. Knockdown of HOXD-AS2 may reduce the growth of glioma, which may provide a new avenue for treatment.

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Section: Introductionmentioning

confidence: 99%

Knockdown of lncRNA HOXD-AS2 Improves the Prognosis of Glioma Patients by Inhibiting the Proliferation and Migration of Glioma Cells

Chen

Zhao

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…HOXD-AS2 can affect the invasion and apoptosis of gliomas by targeting miR-3681-5p and activating the metastasis associated in lung adenocarcinoma Transcript 1 ( MALT1 ) through competing endogenous RNA (ceRNA) mechanism [ 19 ]. Moreover, HOXD-AS2 inhibits the PI3K/Akt signaling pathway by targeting the neighboring gene HOXD8 and acts as a tumor suppressor gene in gastric cancer [ 20 ]. Overall, there are few studies on HOXD-AS2 , particularly the upstream mechanism of HOXD-AS2 .…”

Section: Introductionmentioning

confidence: 99%

Production and Stabilization of Specific Upregulated Long Noncoding RNA HOXD-AS2 in Glioblastomas Are Mediated by TFE3 and miR-661, Respectively

Qin¹,

Qi²,

Zhang³

et al. 2022

IJMS

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Differential expression of long noncoding RNAs (lncRNA) plays a key role in the development of gliomas. Because gliomas are the most common primary central nervous system tumor and glioblastomas have poor prognosis, it is urgent to develop new diagnostic methods. We have previously reported that lncRNA HOXD-AS2, which is specifically up-regulated in gliomas, can activate cell cycle and promote the development of gliomas. It is expected to be a new marker for molecular diagnosis of gliomas, but little is known about HOXD-AS2. Here, we demonstrate that TFE3 and miR-661 maintain the high expression level of HOXD-AS2 by regulating its production and degradation. We found that TFE3 acted as a transcription factor binding to the HOXD-AS2 promoter region and raised H3K27ac to activate HOXD-AS2. As the cytoplasmic-located lncRNA, HOXD-AS2 could be degraded by miR-661. This process was inhibited in gliomas due to the low expression of miR-661. Our study explains why HOXD-AS2 was specifically up-regulated in gliomas, helps to understand the molecular characteristics of gliomas, and provids insights for the search for specific markers in gliomas.

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“…For example, CRART16 [18], LINC01270 [19] and HOXA10-AS [20] show high expression in GC and exert tumorigenic effects. In contrast, downregulation of CRYM-AS1 [21], MBNL1-AS1 [22], and HOXD-AS2 [23] have been demonstrated in GC and are capable of inhibiting cancer progression. However, little is known regarding the role of TMEM147-AS1 in GC.…”

Section: Discussionmentioning

confidence: 94%

Long noncoding RNA TMEM147-AS1 serves as a microRNA-326 sponge to aggravate the malignancy of gastric cancer by upregulating SMAD5

QIN¹,

JIANG²,

ZHU³

et al. 2021

Oncology Research

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The abnormal expression of long noncoding RNAs (lncRNAs) is frequently observed in gastric cancer (GC) and considered an important driving force in GC progression. However, little is known regarding the involvement of TMEM147-AS1 in GC. Therefore, we examined TMEM147-AS1 expression in GC and determined its prognostic value. In addition, TMEM147-AS1 expression was depleted to identify the functional changes in response to TMEM147-AS1 deficiency. Using the cancer genome atlas dataset and our own cohort, we identified a strong expression of TMEM147-AS1 in GC. Increased TMEM147-AS1 levels in GC showed a significant association with poor prognosis. TMEM147-AS1 interference resulted in the inhibition of GC cell proliferation, colony-forming, migration, and invasion in vitro. Additionally, depletion of TMEM147-AS1 restricted the growth of GC cells in vivo.Mechanistically, TMEM147-AS1 functioned as a microRNA-326 (miR-326) sponge. Furthermore, SMAD family member 5 (SMAD5) was experimentally validated as the functional effector of miR-326. TMEM147-AS1 was demonstrated to sequester miR-326 away from SMAD5; consequently, knocking down TMEM147-AS1 downregulated SMAD5 levels in GC cells. The functional suppression of miR-326 or reintroduction of SMAD5 effectively reversed the attenuated behavior of GC cells caused by TMEM147-AS1 downregulation. In summary, TMEM147-AS1 exhibits tumorigenic activities in GC, which is likely the result of an altered miR-326/SMAD5 axis. Therefore, targeting TMEM147-AS1/miR-326/SMAD5 may represent a target for the treatment of GC.

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Decreased expression of the long non-coding RNA HOXD-AS2 promotes gastric cancer progression by targeting HOXD8 and activating PI3K/Akt signaling pathway

Cited by 14 publications

References 29 publications

Knockdown of lncRNA HOXD-AS2 Improves the Prognosis of Glioma Patients by Inhibiting the Proliferation and Migration of Glioma Cells

Knockdown of lncRNA HOXD-AS2 Improves the Prognosis of Glioma Patients by Inhibiting the Proliferation and Migration of Glioma Cells

Production and Stabilization of Specific Upregulated Long Noncoding RNA HOXD-AS2 in Glioblastomas Are Mediated by TFE3 and miR-661, Respectively

Long noncoding RNA TMEM147-AS1 serves as a microRNA-326 sponge to aggravate the malignancy of gastric cancer by upregulating SMAD5

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