Dysregulated lncRNA-UCA1 contributes to the progression of gastric cancer through regulation of the PI3K-Akt-mTOR signaling pathway

Li, Chengyun; Liang, Geyu; Sui, Jing; Yang, Sheng; Xu, Siyi

doi:10.1016/j.toxlet.2017.07.663

Cited by 8 publications

(15 citation statements)

References 26 publications

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“…Stepwise mechanistic studies revealed ARAP1-AS1 enhanced c-Myc translation through competitively binding to PSF and dissociating PSF/ PTB complex, thereby promoting CC progression (Figure A growing body of evidence suggests that lncRNA is an effective biomarker of cancer. 16 For instance, LncRNA SOX2-OT, 17 EGFR-AS1, 18 LOC101928316, 19 and ZFAS1 20 were, respectively, identified as diagnostic or prognostic biomarkers for osteosarcoma, squamous cell carcinoma, gastric cancer, and colorectal cancer. In this study, we found that CC patients with high ARAP1-AS1 expression had shorter survival than patients with low ARAP1-AS1 expression, implying that ARAP1-AS1 is a promising prognostic biomarker for CC patients.…”

Section: Discussionmentioning

confidence: 99%

Retracted: Long non‐coding RNA ARAP1‐AS1 promotes tumorigenesis and metastasis through facilitating proto‐oncogene c‐Myc translation via dissociating PSF/PTB dimer in cervical cancer

Zhang

Wang

2020

Cancer Medicine

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Long non‐coding RNA (lncRNA) is emerging as a pivotal regulator in tumorigenesis and aggressive progression. Here, we focused on an oncogenic lncRNA, ARAP1 antisense RNA 1 (ARAP1‐AS1), which was notably upregulated in cervical cancer (CC) tissues, cell lines and serum. High ARAP1‐AS1 expression was closely associated with larger tumor size, advanced FIGO stage as well as lymph node metastasis. Importantly, it was identified as an effective diagnostic and prognostic biomarker for CC. In vitro and in vivo assays showed that knockdown of ARAP1‐AS1 inhibited, while overexpression of ARAP1‐AS1 promoted CC cell growth and dissemination. Stepwise mechanistic dissection unveiled that ARAP1‐AS1 could directly interact with PSF to release PTB, resulting in accelerating the internal ribosome entry site (IRES)‐driven translation of proto‐oncogene c‐Myc, thereby facilitating CC development and progression. Moreover, c‐Myc was able to transcriptionally activate ARAP1‐AS1 by directly binding to the E‐box motif located on ARAP1‐AS1 promoter. Taken together, our findings clearly reveal the crucial role of ARAP1‐AS1 in CC tumorigenesis and metastasis via regulation of c‐Myc translation, targeting ARAP1‐AS1 and its related regulatory loop implicates the therapeutic possibility for CC patients.

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Section: Discussionmentioning

confidence: 99%

Retracted: Long non‐coding RNA ARAP1‐AS1 promotes tumorigenesis and metastasis through facilitating proto‐oncogene c‐Myc translation via dissociating PSF/PTB dimer in cervical cancer

Zhang

Wang

2020

Cancer Medicine

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“…Gastric cancer (GC) is a malignant tumor and has the highest morbidity and mortality in Asian countries; UCA1 is positively associated with GC proliferation and invasion [62]. UCA1 could significantly promote cell migration and inhibit apoptosis in GC cell lines SUN-216 and SGC-7091 via inhibition of miR-182, whose downstream target is tissue inhibitors of metalloproteinase 2 (TIMP2) [63].…”

Section: Gastrointestinal Cancersmentioning

confidence: 99%

Crosstalk between the lncRNA UCA1 and microRNAs in cancer

Xuan

Zhang

et al. 2019

FEBS Letters

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Long non-coding RNAs (lncRNAs) are a major subset of highly conserved non-coding RNAs (ncRNAs) that consist of at least 200 nucleotides and have limited protein-coding potential. Cumulative data have shown that lncRNAs are deregulated in many types of cancer and may control pathophysiological processes of cancer at various levels, including transcription, post-transcription and translation. Recently, lncRNAs have been demonstrated to interact with microRNAs (miRNAs), another major subset of ncRNAs, which regulate physiological and pathological processes by inhibiting target mRNA translation or promoting mRNA degradation. The lncRNA urothelial carcinomaassociated 1 (UCA1) has recently gained much attention as it is overexpressed in many types of cancer and is involved in carcinogenesis. Here, we review the crosstalk between UCA1 and miRNAs during the pathogenesis of cancer, with a focus on cancer-cell proliferation, invasion, drug resistance, and metabolism.

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“…Meanwhile, lncRNA UCA1 has also been reported to regulate phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway and their downstream mediators [49]. e overexpressed lncRNA UCA1 increased the expression levels of key molecules in the PI3K/ AKT/mTOR signaling pathway, including AKT serine/threonine kinase 3 (AKT3), phosphorylated mammalian target of rapamycin (p-mTOR), and ribosomal protein S6 kinase (S6K), while reducing the eukaryotic translation initiation factor 4E (EIF4E) protein levels in GC cells [49]. Consequently, the regulation of these proteins promoted GC cell growth and proliferation [49].…”

Section: Gastricmentioning

confidence: 99%

Long Noncoding RNA UCA1 in Gastrointestinal Cancers: Molecular Regulatory Roles and Patterns, Mechanisms, and Interactions

Ramli

Sim

Guad

et al. 2021

Journal of Oncology

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The rising trend of gastrointestinal (GI) cancer has become a global burden due to its aggressive nature and poor prognosis. Long noncoding RNAs (lncRNAs) have recently been reported to be overexpressed in different GI cancers and may contribute to cancer progression and chemoresistance. They are featured with more than 200 nucleotides, commonly polyadenylated, and lacking an open reading frame. LncRNAs, particularly urothelial carcinoma-associated 1 (UCA1), are oncogenes involved in regulating cancer progression, such as cell proliferation, invasion, migration, and chemoresistance, particularly in GI cancer. This review was aimed to present an updated focus on the molecular regulatory roles and patterns of lncRNA UCA1 in progression and chemoresistance of different GI cancers, as well as deciphering the underlying mechanisms and its interactions with key molecules involved, together with a brief presentation on its diagnostic and prognostic values. The regulatory roles of lncRNA UCA1 are implicated in esophageal cancer, gastric cancer, pancreatic cancer, hepatobiliary cancer, and colorectal cancer, where they shared similar molecular mechanisms in regulating cancer phenotypes and chemoresistance. Comparatively, gastric cancer is the most intensively studied type in GI cancer. LncRNA UCA1 is implicated in biological roles of different GI cancers via interactions with various molecules, particularly microRNAs, and signaling pathways. In conclusion, lncRNA UCA1 is a potential molecular target for GI cancer, which may lead to the development of a novel chemotherapeutic agent. Hence, it also acts as a potential diagnostic and prognostic marker for GI cancer patients.

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Dysregulated lncRNA-UCA1 contributes to the progression of gastric cancer through regulation of the PI3K-Akt-mTOR signaling pathway

Cited by 8 publications

References 26 publications

Retracted: Long non‐coding RNA ARAP1‐AS1 promotes tumorigenesis and metastasis through facilitating proto‐oncogene c‐Myc translation via dissociating PSF/PTB dimer in cervical cancer

Retracted: Long non‐coding RNA ARAP1‐AS1 promotes tumorigenesis and metastasis through facilitating proto‐oncogene c‐Myc translation via dissociating PSF/PTB dimer in cervical cancer

Crosstalk between the lncRNA UCA1 and microRNAs in cancer

Long Noncoding RNA UCA1 in Gastrointestinal Cancers: Molecular Regulatory Roles and Patterns, Mechanisms, and Interactions

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