The Interaction Between Long Non-coding RNA HULC and MicroRNA-622 via Transfer by Extracellular Vesicles Regulates Cell Invasion and Migration in Human Pancreatic Cancer

Takahashi, Kenji; Koyama, Kazuya; Ota, Yu; Iwamoto, Hidetaka; Yamakita, Keisuke; Fujii, Satoshi; Kitano, Yohei

doi:10.3389/fonc.2020.01013

Cited by 34 publications

(25 citation statements)

References 40 publications

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“…Briefly, HULC promotes cell proliferation of different kinds of tumor cells. 25 , 28 , 29 For instance, overexpression of HULC promotes cell proliferation in lung cancer by upregulating sphingosine kinase 1. 19 In contrast, knockdown of HULC resulted in the decreased proliferation of both osteosarcoma and hepatocellular carcinoma cancer cells.…”

Section: Discussionmentioning

confidence: 99%

<p>LncRNA PTCSC3 and lncRNA HULC Negatively Affect Each Other to Regulate Cancer Cell Invasion and Migration in Gastric Cancer</p>

Cai

Yang

Sun

et al. 2020

CMAR

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Background: LncRNA PTCSC3 (PTCSC3) inhibits thyroid cancer cervical carcinoma and glioma, while its roles in gastric cancer are unknown. Studies have reported that HULC could serve as a potential biomarker for the diagnosis and prognosis of gastric cancer (GC). Our study aimed to investigate the potential interaction between PTCSC3 and HULC in gastric cancer. Methods: This study enrolled 77 gastric cancer patients at the First Affiliated Hospital of Anhui Medical University from January 2016 to January 2018. RT-qPCR was performed to analyze gene expression levels. Cell transfections were carried out to evaluate gene interactions. Transwell assays and wound healing assays were used to analyze the effects of transfection on cell invasion and migration. Western blotting was also used to illustrate the possibility that lncRNA PTCSC3 and lncRNA HULC negatively affected each other through WNT signal path. Results: We showed that PTCSC3 was downregulated in tumor tissues of gastric cancer patients in comparison to that in adjacent healthy tissues, and an inverse correlation between the expression levels of PTCSC3 and AJCC stage was observed. LncRNA HULC (HULC) was upregulated in tumor and inversely correlated with PTCSC3 in tumor tissues. Overexpression of PTCSC3 mediated the inhibition of HULC, while overexpression of HULC also mediated the inhibition of PTCSC3. PTCSC3 inhibited, while HULC promoted invasion and migration of gastric cancer cells. In addition, overexpression of HULC attenuated the effects of overexpression of PTCSC3. However, overexpression of PTCSC3 showed no significant effects on cell proliferation. We also found that PTCSC3/HULC affected each other to regulate cell invasion and migration through the Wnt/β-catenin signaling. Conclusion: Therefore, overexpression of PTCSC3 inhibited the invasion and migration of gastric cancer cells, and the function of PTCSC3 is associated with HULC.

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Section: Discussionmentioning

confidence: 99%

<p>LncRNA PTCSC3 and lncRNA HULC Negatively Affect Each Other to Regulate Cancer Cell Invasion and Migration in Gastric Cancer</p>

Cai

Yang

Sun

et al. 2020

CMAR

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“…It has been demonstrated by our group and others that microRNAs (miRs) represent powerful small RNA molecules that modulate drug resistance related features in HCC [ 10 , 24 ]. In recent years, miR-622 has emerged as one of the most promising tumorsuppressive microRNAs, which is underscored by multiple studies addressing its potent role in diverse types of cancer [ 6 , 10 , 22 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Combined De-Repression of Chemoresistance Associated Mitogen-Activated Protein Kinase 14 and Activating Transcription Factor 2 by Loss of microRNA-622 in Hepatocellular Carcinoma

Fritz

Malek

Gaza

et al. 2021

Cancers

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Chemoresistance is a major hallmark driving the progression and poor prognosis of hepatocellular carcinoma (HCC). Limited chemoresponse of HCC was demonstrated to be mediated by mitogen-activated protein kinase 14 (MAPK14) and activating transcription factor 2 (ATF2). Recently, we have demonstrated loss of control of RAS-RAF-ERK-signaling as a consequence of miR-622 downregulation in HCC. However, the majority of target genes of this potent tumorsuppressive microRNA had remained elusive. The MAPK14-ATF2-axis represents a collateral pathway ensuring persisting ERK-activation in the presence of sorafenib-mediated RAF-inhibition. In contrast to the function of the MAPK14-ATF2-axis, both the expression and regulation of MAPK14 and ATF2 in human HCC remained to be clarified. We found combined overexpression of MAPK14 and ATF2 in human HCC cells, tissues and in sorafenib resistant cell lines. High expression of MAPK14 and ATF2 was associated with reduced overall survival in HCC patients. Deciphering the molecular mechanism promoting combined upregulation of MAPK14 and ATF2 in HCC, we revealed that miR-622 directly targets both genes, resulting in combined de-repression of the MAPK14-ATF2-axis. Together, miR-622 represents a superior regulator of both RAS-RAF-ERK as well as MAPK14-ATF2-signaling pathways in liver cancer.

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“…Another recent study revealed that miR-133b targets HULC directly and attenuates PDAC cell invasion and migration by inhibiting HULC expression highlighting its value as a potential therapeutic target for PDAC [126] . Moreover, overexpression of miR-622, which was significantly downregulated by transforming growth factor beta (TGF-β) in a panel of PDAC cells, significantly reduced cell invasion and migration whereas inhibition of miR-622 increased HULC expression and promoted EMT signalling, invasion, and migration of PDAC cells [127] . Upregulation of HULC was significantly correlated with large tumour size, advanced lymph node metastasis, and vascular invasion; it may serve as an independent predictor for overall survival in PDAC [128] .…”

Section: Lncrnas In Pdacmentioning

confidence: 99%

“…There are a few therapeutic approaches for regulating lncRNAs either by transcript targeting or functional inhibition including (1) small interfering RNA/short hairpin RNA, (2) CRISPR-Cas9, (3) antisense oligonucleotides, (4) morpholino oligonucleotides, (5) Locked Nucleic Acid Gapmers, (6) small molecule inhibitors, (7) exploiting lncRNA promoters [119] . In a recent study, Takahashi and associates (2020) showed that overexpression of miR-622 via miR mimics, as a miR downregulated by TGF-β , could downregulate HULC and suppress invasion and migration by inhibiting EMT signalling via extracellular vesicle transfer [127] . In contrast, inhibition of miR-622 increased HULC expression and promoted epithelial-mesenchymal transition signalling, invasion, and migration of PDAC cells [127] .…”

Section: Current and Potential Therapy Approaches By Using Non-coding Rmentioning

confidence: 99%

“…In a recent study, Takahashi and associates (2020) showed that overexpression of miR-622 via miR mimics, as a miR downregulated by TGF-β , could downregulate HULC and suppress invasion and migration by inhibiting EMT signalling via extracellular vesicle transfer [127] . In contrast, inhibition of miR-622 increased HULC expression and promoted epithelial-mesenchymal transition signalling, invasion, and migration of PDAC cells [127] . The potential of using the aforementioned strategies that would induce gain/loss-of-function to target lncRNAs is promising and enormous although modifying the expression levels of functional lncRNAs in vivo may present another level of difficulty due to their secondary structures [127] .…”

Section: Current and Potential Therapy Approaches By Using Non-coding Rmentioning

confidence: 99%

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Non-coding RNAs in pancreatic ductal adenocarcinoma: New approaches for better diagnosis and therapy

Mortoglou

Tabin

Arısan

et al. 2021

Translational Oncology

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Highlights Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, which is usually diagnosed at an advanced stage. Non-coding RNAs (ncRNAs) have been recognized to play a central role in PDAC pathogenesis and could be used as biomarkers for PDAC. microRNAs (miRs) can act either as oncogenes or tumour suppressors in PDAC. Long non-coding RNAs (lncRNAs) are around 25% of the total RNA distribution in the human cell and their deregulation is widely implicated in PDAC carcinogenesis. Circular RNAs (circRNAs) can be potential novel biomarkers and therapeutic targets for PDAC diagnosis and treatment via their function as miR molecular "sponges", RNA-binding protein (RBP) sponges, protein translators and gene transcription regulators.

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The Interaction Between Long Non-coding RNA HULC and MicroRNA-622 via Transfer by Extracellular Vesicles Regulates Cell Invasion and Migration in Human Pancreatic Cancer

Cited by 34 publications

References 40 publications

<p>LncRNA PTCSC3 and lncRNA HULC Negatively Affect Each Other to Regulate Cancer Cell Invasion and Migration in Gastric Cancer</p>

<p>LncRNA PTCSC3 and lncRNA HULC Negatively Affect Each Other to Regulate Cancer Cell Invasion and Migration in Gastric Cancer</p>

Combined De-Repression of Chemoresistance Associated Mitogen-Activated Protein Kinase 14 and Activating Transcription Factor 2 by Loss of microRNA-622 in Hepatocellular Carcinoma

Non-coding RNAs in pancreatic ductal adenocarcinoma: New approaches for better diagnosis and therapy

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