High Expression of Long Noncoding RNA HOTAIRM1 is Associated with the Proliferation and Migration in Pancreatic Ductal Adenocarcinoma

Luo, Yongyun; He, Yaqin; Ye, Xiaoping; Song, Jianjun; Wang, Qi; Yukui, LI; Xie, Xiaoxiao

doi:10.1007/s12253-018-00570-4

Cited by 32 publications

(27 citation statements)

References 45 publications

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“…HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) is a lncRNA with a length of 1052 bp. It was recently found to participate in various cancers, such as gastrointestinal malignancies [13][14][15][16] , breast cancer 17 , lung cancer 18 , glioblastoma multiforme 19 , and acute myeloid leukemia 20,21 . Of note, HOTAIRM1 is under-expressed in colorectal cancer 13 and gastric cancer 14 .…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion

Chai

et al. 2020

Cell Death Dis

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The long noncoding RNA (lncRNA), HOX antisense intergenic RNA myeloid 1 (HOTAIRM1), has been shown to act as a tumor suppressor in various human cancers. However, the overall biological roles and clinical significance of HOTAIRM1 in papillary thyroid cancer (PTC) have not been investigated. In this study, we used quantitative reverse transcription PCR (qRT-PCR) to show that HOTAIRM1 was significantly downregulated in PTC tissues and low HOTAIRM1 expression levels were associated with lymph node metastasis and advanced TNM stage. We performed Cell Counting Kit-8, plate colony-formation, flow cytometric apoptosis, transwell, and scratch wound healing assays. Overexpression of HOTAIRM1 was found to inhibit PTC cell proliferation, invasion, and migration in vitro. Additionally, we identified miR-107 as a target of HOTAIRM1 using online bioinformatics tools. Dual-luciferase reporter gene and RNA immunoprecipitation assays were used to confirm that HOTAIRM1 acted as a competing endogenous RNA of miR-107. Furthermore, enhancement of miR-107 could potentially reverse the effects of HOTAIRM1 overexpression in vitro. Inhibition of miR-107 suppressed PTC cell proliferation, invasion, and migration in vitro. HOTAIRM1 overexpression and miR-107 inhibition impaired tumorigenesis in vivo in mouse xenografts. Bioinformatics prediction and a dual-luciferase reporter gene assay demonstrated the binding between miR-107 and the 3′-untranslated region of TDG. The results of qRT-PCR and western blotting assays suggested that HOTAIRM1 could regulate the expression of TDG in an miR-107meditated manner. In conclusion, we validated HOTAIRM1 as a novel tumor-suppressor lncRNA in PTC and proposed that the HOTAIRM1/miR-107/TDG axis may serve as a therapeutic target for PTC.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion

Chai

et al. 2020

Cell Death Dis

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“…For instance, HOTAIRM1 inhibits tumorigenesis by forming ceRNA networks in colorectal cancer, head and neck tumors, gastric cancer, and hepatocellular carcinoma [10–12, 27]. Conversely, HOTAIRM1 promotes breast cancer, lung cancer, and pancreatic ductal adenocarcinoma by directly regulating HOXA1 expression [13, 14, 28, 29]. As a fetal lncRNA [30], HOTAIRM1 is upregulated in glioma [31, 32].…”

Section: Discussionmentioning

confidence: 99%

“…HOTAIRM1 functions as a tumor suppressor in colorectal, head and neck, gastric, and lung cancers by sponging micro (mi)RNAs and regulating immunosuppressive myeloid-derived suppressor cells [10–13]. However, HOTAIRM1 was also shown to promote cell proliferation and migration in pancreatic ductal adenocarcinoma [14]. Therefore, additional studies are needed to clarify the role of HOTAIRM1 in cancer.…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA, HOTAIRM1, promotes glioma malignancy by forming a ceRNA network

Liang

Guan

et al. 2019

Aging

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Long non-coding RNAs play critical roles in tumorigenesis and the immune process. In this study, RNA sequencing data for 946 glioma samples from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas databases were analyzed to evaluate the prognostic value and function of homeobox A transcript antisense RNA myeloid-specific (HOTAIRM)1. HOTAIRM1 expression was associated with clinical and molecular features of glioma: patients with high HOTAIRM1 expression were more likely to be classified as malignant cases, and elevated HOTAIRM1 level was associated with shorter survival time in subgroups stratified by clinical and molecular features. A multivariate Cox regression analysis showed that HOTAIRM1 was an independent prognostic factor for patient outcome. In vitro experiments revealed that HOTAIRM1 knockdown suppressed the malignant behavior of glioma and increased tumor sensitivity to temozolomide. The results of an in silico analysis indicated that HOTAIRM1 promotes the malignancy of glioma by acting as a sponge for microRNA (miR)-129-5p and miR-495-3p. HOTAIRM1 overexpression was also associated with immune activation characterized by enhanced T cell-mediated immune and inflammatory responses. These results suggest that HOTAIRM1 is a prognostic biomarker and potential therapeutic target in glioma.

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“…For example, in hepatocellular carcinoma and gastric cancer, HOTAIRM1 prevents cancer progression by suppressing signaling cascades such as the Wnt and the PI3K/AKT pathways [32,33]. On the other hand, high expression of HOTAIRM1 has been associated with oncogenicity in pancreatic ductal carcinoma by promoting proliferative and migratory abilities [25]. In addition, the role of HOTAIRM1 in occluding epigenetic factors like G9a and EZH2, and reducing repressive histone enrichments have been reported in glioblastoma multiforme [26].…”

Section: Discussionmentioning

confidence: 99%

“…Within the HOXA cluster is a long non-coding RNA, HOTAIRM1, located between HOXA1 and HOXA2. The role of HOTAIRM1 as an oncogenic factor has been described in several cancers [25,26], and the function of HOTAIRM1 as a regulator of the oncogene HOXA1 has been previously described in glioblastoma multiforme [26]. However, the regulatory role of HOTAIRM1 on HOXA1 transcription in breast cancer, more specifically tamoxifen-resistant breast cancer, remains unknown.…”

Section: Ivyspringmentioning

confidence: 99%

The LncRNA HOTAIRM1 Promotes Tamoxifen Resistance by Mediating HOXA1 Expression in ER+ Breast Cancer Cells

Kim¹,

Oh²,

Lee³

et al. 2020

J. Cancer

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Breast cancer is one of the most commonly diagnosed cancers in women worldwide. Approximately 40% of patients with breast cancer acquire endocrine resistance following therapy with tamoxifen. Many explanations for the development of endocrine resistance have been put forward, one of them being the dysregulation of long non-coding RNAs (lncRNAs). The lncRNA HOTAIRM1, known to be involved in myelopoiesis as well as transcriptional regulation of the HOXA genes in embryonic stem cells, is also expressed in breast cancer cells. This study explored the molecular mechanisms of HOTAIRM1 involved in acquired tamoxifen resistance. We showed that HOTAIRM1 and HOXA1 are concurrently up-regulated in tamoxifen-resistant MCF7 (TAMR) cells. Knockdown of HOTAIRM1 down-regulated HOXA1 expression and restored sensitivity to tamoxifen. In addition, the knockdown of HOXA1 showed similar effects, suggesting that the HOTAIRM1/HOXA1 axis regulates tamoxifen resistance. Furthermore, we showed that HOTAIRM1 directly interacts with EZH2 and prevents the PRC2 complex from binding and depositing H3K27me3 on the putative promoter of HOXA1. Together, our findings suggest that HOXA1 and its neighboring lncRNA, HOTAIRM1, might serve as potential therapeutic targets for ER+ breast cancer patients who have acquired tamoxifen resistance.

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High Expression of Long Noncoding RNA HOTAIRM1 is Associated with the Proliferation and Migration in Pancreatic Ductal Adenocarcinoma

Cited by 32 publications

References 45 publications

RETRACTED ARTICLE: The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion

RETRACTED ARTICLE: The HOTAIRM1/miR-107/TDG axis regulates papillary thyroid cancer cell proliferation and invasion

Long non-coding RNA, HOTAIRM1, promotes glioma malignancy by forming a ceRNA network

The LncRNA HOTAIRM1 Promotes Tamoxifen Resistance by Mediating HOXA1 Expression in ER+ Breast Cancer Cells

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