Knockdown of lncRNA HNF1A-AS1 inhibits oncogenic phenotypes in colorectal carcinoma

Zhu, Weixing; Zhuang, Peipei; Song, Wen; Duan, Shiyu; Xu, Qiong; Peng, Man; Zhou, Jun

doi:10.3892/mmr.2017.7175

Cited by 20 publications

(26 citation statements)

References 17 publications

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“…Genome-wide analysis has demonstrated that non-protein coding RNAs occupy >90% of the human genome's transcriptional output in genome-wide analysis (18); in addition, the detailed molecular mechanisms for the majority of lncRNAs have yet to be elucidated. Accumulating evidence has illustrated that lncRNAs serve essential roles during gene regulatory processes and are involved in a number of biological functions, including cell proliferation and differentiation in normal and transformed cells (19,20). Emerging evidence has further demonstrated that dysregulation of lncRNAs is involved in epigenetic regulatory mechanisms underlying physiological and pathological processes; therefore, lncRNAs serve as novel regulators in progressive and uncontrolled tumor growth, EMT processes and metastasis (12,21,22).…”

Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA DLX6‑AS1 is associated with malignant progression and promotes proliferation and invasion in esophageal squamous cell carcinoma

Wang

Yang

et al. 2018

Mol Med Report

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Despite being one of the most prevalent and fatal types of cancer worldwide, the biological details of esophageal squamous cell carcinoma (ESCC) remain unknown. Recent studies have demonstrated the crucial roles of long non-coding RNAs (lncRNAs) in diverse biological processes including cancer initiation, progression and metastasis. The aim of the present study was to assess the expression profile of distal-less homeobox 6 antisense RNA 1 (DLX6-AS1) in ESCC tissues and its contributions to ESCC cell proliferation, apoptosis and invasion. The expression of DLX6-AS1 in a series of ESCC samples and paired adjacent noncancerous tissues was evaluated by reverse transcription-quantitative polymerase chain reaction. Cell proliferation, apoptosis, wound healing and Transwell invasion assays were performed to evaluate the roles of DLX6-AS1 in the ESCC cell lines EC109 and KYSE30 transfected with DLX6-AS1 small interfering RNA (siRNA). Compared with the paired adjacent noncancerous tissues, DLX6-AS1 expression was upregulated in the ESCC tissues and significantly associated with differentiation status, Tumor-Node-Metastasis stage, distant metastasis, and lymph node metastasis. Knockdown of DLX6-AS1 significantly suppressed cell proliferation, invasion and migration abilities, and enhanced the apoptotic rate in the two ESCC cell lines. Furthermore, western blot assays revealed that silencing DLX6-AS1 partly influenced the epithelial-mesenchymal transition process in ESCC cells. These results imply that the oncogenic function of DLX6-AS1 may be a novel candidate target for treating human ESCC.

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Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA DLX6‑AS1 is associated with malignant progression and promotes proliferation and invasion in esophageal squamous cell carcinoma

Wang

Yang

et al. 2018

Mol Med Report

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“…The lncRNA HNF1A antisense RNA 1 (HNF1A-AS1), as an oncogene, was involved in cell progression and metabolism in many cancers, such as lung adenocarcinoma, colorectal carcinoma, oesophageal adenocarcinoma, nonsmall cell lung cancer, bladder cancer and hepatocellular carcinoma. [18][19][20][21][22][23] Zhao et al demonstrated that induction of HNF1A-AS contributed to cell proliferation and metastasis through activating Wnt/β-catenin signaling pathway in osteosarcoma. 24 In addition, lncRNA HNF1A-AS1 has been determined to be a novel diagnostic predictor for prognosis of cancers.…”

Section: Introductionmentioning

confidence: 99%

<p>HNF1A-AS1 Regulates Cell Migration, Invasion and Glycolysis via Modulating miR-124/MYO6 in Colorectal Cancer Cells</p>

Guo¹,

Zhang²,

Liu³

et al. 2020

OTT

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Background: Accumulating evidence determined that lncRNAs play multiple roles in cell progression in colorectal cancer (CRC). Long noncoding RNA (lncRNA) hepatocyte nuclear factor 1 homeobox A (HNF1A)-antisense RNA 1 (AS1) has been identified to affect cell growth and disease diagnosis in various cancers, including CRC. However, the underlying regulatory mechanism of HNF1A-AS1 in cell progression and glycolysis has not been fully explored in CRC. Materials and Methods: The expression of HNF1A-AS1, microRNA-124 (miR-124) and Myosins of class VI (MYO6) was detected using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The analysis of glucose consumption, lactate production and hexokinase 2 (HK2) protein level was used to assess glycolysis in cells. The protein level of HK2 and MYO6 was measured with Western blot. Cell migration and invasion were evaluated using the transwell assay. The relationship among HNF1A-AS1, miR-124 and MYO6 was determined via luciferase reporter and RNA immunoprecipitation (RIP) assay. Results: In this study, we found that HNF1A-AS1 was upregulated in CRC tissues and cell lines. Functional experiments determined that reduction of HNF1A-AS1 or promotion of miR-124 inhibited cell migration and invasion as well as glycolysis in CRC cells. What' more, luciferase reporter assay manifested that miR-124 was a target of HNF1A-AS1 and MYO6 was a target mRNA of miR-124 in CRC cells. Additionally, reverse experiments showed that the effects of si-HNF1A-AS1 on colorectal cancer cells were impaired by anti-miR-124 and the effects of high miR-124 expression on CRC cells were rescued by upregulating MYO6. HNF1A-AS1 regulated MYO6 expression via targeting miR-124 in CRC cells. Conclusion: In this study, we first found that HNF1A-AS1 regulated cell migration, invasion and glycolysis via modulating miR-124/MYO6 in CRC cells.

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“…Long non‐coding RNAs (LncRNAs) are generally defined as RNA molecules larger than 200 nucleotides in length that do not have encoding functions, and are usually determined by means of bioinformatics . As a type of regulating RNA in gene expression, lncRNAs play their roles by controlling the expression of their target genes and participating in the process of extensive biological activities, such as embryogenesis, tissue development, and diseases . Numerous studies have confirmed the strong correlations between lncRNAs and various human diseases, including cancers, Alzheimer's disease, and cardiovascular diseases .…”

Section: Introductionmentioning

confidence: 99%

“…14 As a type of regulating RNA in gene expression, lncRNAs play their roles by controlling the expression of their target genes and participating in the process of extensive biological activities, such as embryogenesis, tissue development, and diseases. [15][16][17][18] Numerous studies have confirmed the strong correlations between lncRNAs and various human diseases, including cancers, 19 Alzheimer's disease, 20 and cardiovascular diseases. 21 Some lncRNAs are reported to participate and play critical roles in tumorigenesis, including the generation, growth, and metastasis of cancers from several types of tissue origins.…”

mentioning

confidence: 99%

MALAT1 promotes the colorectal cancer malignancy by increasing DCP1A expression and miR203 downregulation

Zhu

Tao

et al. 2018

Molecular Carcinogenesis

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The long non-coding RNA MALAT1 has been proved to promote the cell proliferation, drug resistance, invasion, and metastasis of colorectal cancer (CRC) in vitro and in vivo by regulating the expression of various oncogenes and their protein products. Our previous work discovered that the expression of the mRNA-decapping enzymes 1a (DCP1A) is upregulated in CRCs. However, the relationships between MALAT1 and DCP1A in the development of CRC and the underlying mechanisms are still unclear. In this study, we investigated the molecular mechanisms by which MALAT1 and DCP1A may be linked to contribute to the malignancies of CRCs. We found that DCP1A is a direct target molecule of MALAT1. Moreover, by screening the downstream genes of MALAT1, we noticed that microRNA 203(miR203), an oncogene suppressor in numerous cancers, is inversely correlated to both MALAT1 and DCP1A expressions. Following MALAT1 knockdown, we observed overexpression of miR203 accompanied with DCP1A downregulation to a level that reversed the promoted cell proliferation, invasion, and migration in vitro and in vivo, which could be restored by miR203 knockdown or DCP1A overexpression. These results proposed a new molecular mechanism of MALAT-miR203-DCP1A axis which is involved with the development and contributes to the malignancy of colorectal cancers.

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Knockdown of lncRNA HNF1A-AS1 inhibits oncogenic phenotypes in colorectal carcinoma

Cited by 20 publications

References 17 publications

Long non‑coding RNA DLX6‑AS1 is associated with malignant progression and promotes proliferation and invasion in esophageal squamous cell carcinoma

Long non‑coding RNA DLX6‑AS1 is associated with malignant progression and promotes proliferation and invasion in esophageal squamous cell carcinoma

<p>HNF1A-AS1 Regulates Cell Migration, Invasion and Glycolysis via Modulating miR-124/MYO6 in Colorectal Cancer Cells</p>

MALAT1 promotes the colorectal cancer malignancy by increasing DCP1A expression and miR203 downregulation

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