Long Noncoding RNA in Digestive Tract Cancers: Function, Mechanism, and Potential Biomarker

Zeng, Shuo; Xiao, Yufeng; Tang, Bo; Hu, C.; Xie, Rei; Yang, Shiming; Li, Bosheng

doi:10.1634/theoncologist.2014-0475

Cited by 31 publications

(21 citation statements)

References 92 publications

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“…lncRNAs are a major research focus, and their number exceeds that of protein-coding RNAs. An increasing number of lncRNAs that participate in gene regulation are being discovered (16). Ever since the discovery of HOTAIR, an important representative lncRNA, research has shown that it is abnormally expressed in many types of tumors.…”

Section: Discussionmentioning

confidence: 99%

Elevated HOTAIR expression associated with cisplatin resistance in non-small cell lung cancer patients

Liu¹,

Li²,

Gao³

et al. 2016

J. Thorac. Dis.

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Background: This study investigated the mechanism of drug resistance in non-small cell lung cancer (NSCLC) patients. We specifically studied whether long noncoding RNAs influence drug resistance in NSCLC to discover new therapeutic targets to increase the survival rate of drug-resistant NSCLC patients. Methods: Tissue samples were collected from NSCLC patients, and total RNA was isolated for assessment of HOTAIR expression and drug resistance status. MTT assays, tumor sphere formation assays, and western blot were performed to cytologically determine the relationship between HOTAIR expression and cisplatin resistance, as well as to elucidate the potential molecular mechanism involved. Results: HOTAIR expression in tissues of drug-resistant NSCLC patients was higher than that of nondrug-resistant patients. HOTAIR expression was elevated in cisplatin-resistant cell strains (A549/CDDP), and reducing HOTAIR expression increased the sensitivity of A549/CDDP cells to cisplatin. In addition, overexpression of HOTAIR in A549 cells increased resistance to cisplatin. Tumor sphere formation assays showed that the volume of spheres formed by cell strains expressing elevated levels of HOTAIR was greater than that of cell strains with low expression. Western blot experiments showed that elevated expression of HOTAIR upregulated tumor stem cell-related biomarkers and HOTAIR expression was directly related to Klf4 expression.Conclusions: Elevated HOTAIR expression is associated with drug resistance in NSCLC patients and is related to Klf4 upregulation, providing a new therapeutic target for drug-resistant NSCLC patients.

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Section: Discussionmentioning

confidence: 99%

Elevated HOTAIR expression associated with cisplatin resistance in non-small cell lung cancer patients

Liu¹,

Li²,

Gao³

et al. 2016

J. Thorac. Dis.

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“…93 LncRNAs can be targeted therapeutically by a variety of approaches including (i) RNA interference (RNAi)-mediated downregulation of specific lncRNAs; (ii) antisense oligonucleotides (ASO)-based therapy; (iii) plasmid-based therapy; (iv) lncRNA mimics or small-molecule inhibitors; (v) gene therapy, and so on. 94 Although RNAi technology offers immense therapeutic promise due to its high potency, the main obstacle of siRNA/shRNA-based therapeutics remains its poor delivery in vivo . In contrast to RNAi, ASOs are synthetic, short, single-stranded DNAs or RNAs (between 8 and 50 nt), another type of nucleic acid drugs, which are designed with sequence specificity to target lncRNAs.…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Long non-coding RNA regulation of epithelial–mesenchymal transition in cancer metastasis

et al. 2016

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Metastasis is a multistep process starting with the dissemination of tumor cells from a primary site and ending with secondary tumor development in an anatomically distant location. The epithelial–mesenchymal transition (EMT), a process that endows epithelial tumor cells with mesenchymal properties including reduced adhesion and increased motility, is considered a critical step driving the early phase of cancer metastasis. Although significant progress has been made in understanding the molecular characteristics of EMT, the intracellular mechanisms driving transition through the various stages of EMT remain unclear. In recent years, an increasing number of studies have demonstrated the involvement of long non-coding RNAs (lncRNAs) in tumor metastasis through modulating EMT. LncRNAs and their associated signaling networks have now emerged as new players in the induction and regulation of EMT during metastasis. Here we summarize the recent findings and characterizations of several known lncRNAs involved in the regulation of EMT. We will also discuss the potential use of these lncRNAs as diagnostic and prognostic biomarkers as well as therapeutic targets to slow down or prevent metastatic spread of malignant tumors.

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“…It is well known that lncRNAs participate in cancer-associated pathways (7). Although an increasing number of lncRNAs have been reported to functionally regulate the metastatic behavior of GC cells, a large number of lncRNAs require identification, as 70-90% of the human genome transcribes RNA products, whereas protein-coding genes account for only 2% (8). Therefore, the present study focused on an lncRNA, AFAP1-antisense RNA 1 (AFAP1-AS1), which was first observed in esophageal cancer and acted as an oncogene, mediating effects in cell proliferation, migration and invasion (9).…”

Section: Introductionmentioning

confidence: 99%

Long non‑coding RNA AFAP1‑antisense RNA 1 promotes the proliferation, migration and invasion of gastric cancer cells and is associated with poor patient survival

et al. 2018

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Gastric cancer (GC) is the second-leading cause of cancer-associated mortality worldwide. AFAP1-antisense RNA 1 (AFAP1-AS1), a long non-coding RNA (lncRNA), is believed to promote the aggressive progression of cancer; however, its role in GC remains largely unknown. In the present study, the expression of AFAP1-AS1 in GC tissues and cell lines was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Knockdown of AFAP1-AS1 was performed using a lentiviral vector containing a short hairpin RNA. The proliferation of GC cells was measured using Cell Counting kit-8. The migration and invasion of GC cells were analyzed using a QCM Laminin Migration Assay kit and a Cell Invasion Assay kit. The levels of epithelial-mesenchymal transition (EMT)-associated proteins were detected by western blot analysis. The cut-off value of the expression of AFAP1-AS1 was evaluated using receiver operating characteristic (ROC) curves and patient survival rate was analyzed using Kaplan-Meier. The expression of AFAP1-AS1 was significantly increased in the primary tumor tissues of GC patients with lymph node metastasis or tumor node metastasis stage (stage III or IV; P<0.01). ROC curve analysis revealed that the expression of AFAP-AS1, at a cut-off value of 0.5040, could distinguish GC tissues from the matched normal tissues, with an AUC of 0.8802, sensitivity of 81.25% and specificity of 83.75%. The overexpression of AFAP1-AS1 was positively associated with the poor survival rates of GC patients. Furthermore, the downregulation of AFAP1-AS1 significantly inhibited the proliferation, migration and invasion of GC cells (P<0.01). The decrease in AFAP1-AS1 expression significantly suppressed the expression level of N-cadherin protein in GC cells and increased that of E-cadherin. The present study demonstrated that the expression signature of AFAP1-AS1 may serve as a biomarker for the diagnosis and prognosis of GC, and its downregulation may repress the aggressive progression of GC, partially through inhibiting the EMT progress.

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Long Noncoding RNA in Digestive Tract Cancers: Function, Mechanism, and Potential Biomarker

Cited by 31 publications

References 92 publications

Elevated HOTAIR expression associated with cisplatin resistance in non-small cell lung cancer patients

Elevated HOTAIR expression associated with cisplatin resistance in non-small cell lung cancer patients

Long non-coding RNA regulation of epithelial–mesenchymal transition in cancer metastasis

Long non‑coding RNA AFAP1‑antisense RNA 1 promotes the proliferation, migration and invasion of gastric cancer cells and is associated with poor patient survival

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