MiR-216a-5p inhibits tumorigenesis in Pancreatic Cancer by targeting TPT1/mTORC1 and is mediated by LINC01133

Zhang, Jian; Gao, Shengxiang; Zhang, Yandong; Yi, Huixin; Xu, Mengxian; Xu, Jialun; Liu, Huan; Ding, Zhichen; He, Hongbin; Wang, Hongmei; Hao, Zhuo; Sun, Liankun; Liu, Yan; Feng, Wei

doi:10.7150/ijbs.46822

Cited by 38 publications

(40 citation statements)

References 30 publications

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“…LincRNAs interact with proteins, miRNAs, and other molecules to exert their functions 35 . Previous studies suggested that LINC01133 sponges miR‐4784 and miR‐205 to counter miRNA‐mediated gene silencing in cervical cancer and gastric cancer, respectively 36,37 . Our miR‐seq and bioinformatics analyses revealed that LINC01133 sponges miR‐199a‐5p in HCC.…”

Section: Discussionmentioning

confidence: 63%

“…35 Previous studies suggested that LINC01133 sponges miR-4784 and miR-205 to counter miRNA-mediated gene silencing in cervical cancer and gastric cancer, respectively. 36,37 Our miR-seq and bioinformatics analyses revealed that LINC01133 sponges miR-199a-5p in HCC. We also predicted on the basis of bioinformatic analysis that LINC01133 interacts with miR-501-5p, but qRT-PCR revealed that LINC01133 did not affect the expression of miR-501-5p in HCC cells.…”

Section: Discussionmentioning

confidence: 92%

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LINC01133 promotes hepatocellular carcinoma progression by sponging miR‐199a‐5p and activating annexin A2

Yin

Luo

et al. 2021

Clinical & Translational Med

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Background Long noncoding RNAs (lncRNAs) are functionally associated with cancer development and progression. Although gene copy number variation (CNV) is common in hepatocellular carcinoma (HCC), it is not known how CNV in lncRNAs affects HCC progression and recurrence. We aimed to identify a CNV‐related lncRNA involved in HCC progression and recurrence and illustrate its underlying mechanisms and prognostic value. Methods We analyzed the whole genome sequencing (WGS) data of matched cancerous and noncancerous liver samples from 49 patients with HCC to identify lncRNAs with CNV. The results were validated in another cohort of 238 paired HCC and nontumor samples by TaqMan copy number assay. We preformed Kaplan‐Meier analysis and log‐rank test to identify lncRNA CNV with prognostic value. We conducted loss‐ and gain‐of‐function studies to explore the biological functions of LINC01133 in vitro and in vivo. The competing endogenous RNAs (ceRNAs) mechanism was clarified by microRNA sequencing (miR‐seq), quantitative real‐time PCR (qRT‐PCR), western blot, and dual‐luciferase reporter assays. We confirmed the binding mechanism between lncRNA and protein by RNA pull‐down, RNA immunoprecipitation, qRT‐PCR, and western blot analyses. Results Genomic copy numbers of LINC01133 were increased in HCC, which were positively related with the elevated expression of LINC01133. Increased copy number of LINC01133 predicted the poor prognosis in HCC patients. LINC01133 overexpression in HCC cells promoted proliferation and aggressive phenotypes in vitro, and facilitated tumor growth and lung metastasis in vivo, whereas LINC01133 knockdown had the opposite effects. LINC01133 sponged miR‐199a‐5p, resulting in enhanced expression of SNAI1, which induced epithelial‐to‐mesenchymal transition (EMT) in HCC cells. In addition, LINC01133 interacted with Annexin A2 (ANXA2) to activate the ANXA2/STAT3 signaling pathway. Conclusions LINC01133 promotes HCC progression by sponging miR‐199a‐5p and interacting with ANXA2. LINC01133 CNV gain is predictive of poor prognosis in patients with HCC.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 92%

LINC01133 promotes hepatocellular carcinoma progression by sponging miR‐199a‐5p and activating annexin A2

Yin

Luo

et al. 2021

Clinical & Translational Med

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“…To our knowledge, no research related to MIR600HG and AP004608.1 has been published so far and there are only a few studies focusing on the mechanism of LINC00857 in cancers. As for LINC01133, Zhang et al 24 have reported a LINC01133/miR-216a-5p/TPT1/mTORC1 ceRNA axis that regulated tumorigenesis of PAAD. We hoped to further complement the in-depth mechanism experiments for all of these potential lncRNAs in the future.…”

Section: Discussionmentioning

confidence: 99%

<p>Identification and Development of Long Non‐coding RNA Associated Regulatory Network in Pancreatic Adenocarcinoma</p>

Zhu

Gao

Deng³

et al. 2020

OTT

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Background and Aims: Pancreatic adenocarcinoma (PAAD) is the most lethal cancer type around the world. With the in-depth exploration of the function of long non-coding RNAs (lncRNAs), the competing endogenous RNA (ceRNA) mechanism has shown its potential to partially reveal the pathogenesis of PAAD. This study aimed to construct a lncRNA-associated ceRNA network and explore ceRNA regulatory axes with experimental and prognostic value in PAAD. Methods: First, we applied differential expression analysis in the TCGA_PAAD dataset. Then, interaction analysis and survival analysis in multiple RNA interaction databases were conducted to construct a ceRNA network. Finally, a potential regulatory axis was validated using clinical samples and cell lines by quantitative realtime PCR (qRT-PCR). Results: A ceRNA network comprising 13 lncRNAs, 96 miRNAs, and 30 mRNAs was successfully constructed. Survival analysis further narrowed this network to five lncRNAs, three miRNAs, and seven mRNAs, which were significantly associated with patients' overall survival. A potential regulatory axis CASC8-miR-129-5p-TOB1 was further experimentally validated. The expression of these genes was associated with clinicopathological factors and their expression trend was consistent with ceRNA mechanism. Specifically, knockdown of lncRNA-CASC8 led to the overexpression of miR-129-5p and down-regulation of TOB1, while overexpression of CASC8 showed opposite effects. Conclusion: This novel ceRNA regulatory network could provide new insight into the pathogenesis of PAAD. The new regulatory axis CASC8-miR-129-5p-TOB1 might serve as a potential therapeutic target for patients.

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“…LincRNAs interact with proteins, miRNAs, and other molecules to exert their functions [32]. Previous studies suggested that LINC01133 sponges miR-4784 and miR-205 to counter microRNA-mediated gene silencing in cervical cancer and gastric cancer, respectively [33,34]. We revealed that LINC01133 is a sponge of miR-199a-5p in HCC through miR-seq and bioinformatics analyses.…”

Section: Discussionmentioning

confidence: 74%

The Long Non-coding RNA LINC01133 Promotes Hepatocellular Carcinoma Progression by Sponging miR-199a-5p and Activating Annexin A2

Yin

Luo

et al. 2020

Preprint

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Background: Long non-coding RNAs (lncRNAs) have been found to be functionally associated with cancer development and progression. Although copy number variations (CNVs) are common in hepatocellular carcinoma (HCC), little is known about how CNVs in lncRNAs affect HCC progression and recurrence.Methods: We analyzed the whole genome sequencing (WGS) data of matched cancerous and non-cancerous liver samples from 49 patients with HCC to identify lncRNAs with CNVs. The results were validated in another cohort of 238 paired HCC and non-tumor samples by TaqMan copy number assay. Kaplan-Meier analysis and the log-rank test were performed to determine the prognostic value of CNVs in lincRNAs. Loss- and gain-of-function studies were conducted to determine the biological functions of LINC01133 in vitro and in vivo. The competing endogenous RNAs (ceRNAs) mechanism was clarified by microRNA sequencing (miR-seq), quantitative real-time PCR (qRT-PCR), western blot, and dual-luciferase reporter analyses. The protein binding mechanism was confirmed by RNA pull-down, RNA immunoprecipitation (RIP), qRT-PCR, and western blot analyses.Results: Genomic copy number of LINC01133 was increased in HCC, which is positively related with the elevated expression of LINC01133. Increased copy number of LINC01133 predicted the poor prognosis in HCC patients. LINC01133 overexpression promoted proliferation, colony formation, migration, and invasion in vitro, and facilitated tumor growth and lung metastasis in vivo, whereas LINC01133 knockdown had the opposite effects. Mechanistically, LINC01133 acted as a sponge of miR-199a-5p, resulting in enhanced expression of SNAI1, which induced epithelial-mesenchymal transition (EMT) in HCC cells. In addition, LINC01133 interacted with Annexin A2 (ANXA2) to activate ANXA2/STAT3 signaling pathway.Conclusions: LINC01133 promotes HCC progression by sponging miR-199a-5p and interacting with ANXA2. LINC01133 CNV gain is predictive of poor prognosis in HCC patients undergoing curative resection.

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MiR-216a-5p inhibits tumorigenesis in Pancreatic Cancer by targeting TPT1/mTORC1 and is mediated by LINC01133

Cited by 38 publications

References 30 publications

LINC01133 promotes hepatocellular carcinoma progression by sponging miR‐199a‐5p and activating annexin A2

LINC01133 promotes hepatocellular carcinoma progression by sponging miR‐199a‐5p and activating annexin A2

<p>Identification and Development of Long Non‐coding RNA Associated Regulatory Network in Pancreatic Adenocarcinoma</p>

The Long Non-coding RNA LINC01133 Promotes Hepatocellular Carcinoma Progression by Sponging miR-199a-5p and Activating Annexin A2

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