Long non-coding RNAs (lncRNAs) are nucleotide sequences that participate in different biological processes and are associated with different pathologies, including cancer. Long intergenic non-protein-coding RNA 662 (LINC00662) has been reported to be involved in different cancers, including colorectal, prostate, and breast cancer. However, its role in gallbladder cancer has not yet been described. In this article, we hypothesize that LINC00662 has an important role in the acquisition of aggressiveness traits such as a stem-like phenotype, invasion, and chemoresistance in gallbladder cancer. Here, we show that LINC00662 is associated with larger tumor size and lymph node metastasis in patients with gallbladder cancer. Furthermore, we show that the overexpression of LINC00662 promotes an increase in CD133+/CD44+ cell populations and the expression of stemness-associated genes. LINC00662 promotes greater invasive capacity and the expression of genes associated with epithelial-mesenchymal transition. In addition, the expression of LINC00662 promotes resistance to cisplatin and 5-fluorouracil, associated with increased expression of chemoresistance-related ATP-binding cassette (ABC) transporters in gallbladder cancer (GBC) cell lines. Finally, we show that the mechanism by which LINC00662 exerts its function is through a decrease in microRNA 335-5p (miR-335-5p) and an increase in octamer-binding transcription factor 4 (OCT4) in GBC cells. Thus, our data allow us to propose LINC00662 as a biomarker of poor prognosis and a potential therapeutic target for patients with GBC.

Background: Long non-coding RNAs (lncRNAs) are associated with multiple head and neck tumors and play important roles in cancer. This study explored the molecular mechanism of Linc00662 in hypopharyngeal squamous cell carcinoma (HSCC). Methods: Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect gene expression in HSCC tissues. The viability and proliferation of tumor cells were measured using CCK-8 assays. HSCC cell apoptosis was measured using flow cytometry and western blotting. Cell stemness was examined using the sphere formation assay. A xenograft tumor model was established to investigate the role of Linc00662 in vivo. Results: The expression level of Linc00662 in HSCC tissues was significantly higher than that in adjacent normal tissues. The expression of Linc00662 had no significant relationship with the tumor stage. Patients with high Linc00662 expression were found to have shorter overall survival than those with low Linc00662 expression. Linc00662 over-expression promoted cell viability and inhibited apoptosis. Using online databases and a dual luciferase reporter, miR-15b-5p was confirmed as a potential downstream sponge of Linc00662. Moreover, Linc00662 was negatively associated with miR-15b-5p in HSCC cells. Depletion of miR-15b-5p can reverse the function of Linc00662 in vivo and in vitro. Furthermore, Linc00662 promotes tumor growth, which was abolished by miR-15b-5p mimics. Importantly, the stemness of cancer stem cells was mediated by the Linc00662/miR-15b-5p axis. Conclusion: Patients with HSCC with high Linc00662 showed poor prognosis and high Linc00662 induced stemness of tumor cells by targeting miR-15b-5p. Linc00662 may serve as a novel diagnostic and target marker for head and neck squamous cell carcinoma.

Melanoma is a highly malignant tumor in the body. Long non-coding RNAs (lncRNAs) have been reported to be involved in the development of various tumors. Emerging evidence demonstrates the critical role of lncRNAs in melanoma development. In this study, we aimed to investigate the expression, biological function and regulatory mechanism of LINC00662 in melanomas. First, we found that LINC00662 was up-regulated in melanoma tissues and cell lines. High expression of LINC00662 in melanomas was associated with a poor patient prognosis. Silencing of LINC00662 suppressed the proliferation, migration, and invasion of melanoma cells in vitro and in vivo, while overexpression of LINC00662 promoted melanoma cell proliferation in vitro. Bioinformatics analysis, dual-luciferase assay, and RIP assay confirmed that LINC00662 competitively regulated miR-107. Silencing of LINC00662 upregulated miR-107 expression in a melanoma cell line. Inhibition of miR-107 significantly reversed the inhibitory effect of LINC00662 silencing on cell proliferation and migration. Furthermore, POU3F2 was validated as a downstream target of LINC00662/miR107 and was downregulated when LINC00662 was silenced. Overexpressing POU3F2 attenuated the effect of si-LINC00662 on cellular functions. In addition, the results also showed that the β-catenin pathway was involved in a si-LINC00662-induced function in melanoma. Overall, our results confirmed that LINC00662 promoted melanoma progression by sponging miR107 and inducing POU3F2, highlighting the mechanism of the LINC00662/miR-107/POU3F2 axis in melanoma cell proliferation and invasion.

Recurrence and metastasis are major factors associated with the poor prognosis of pancreatic cancer (PC). Previous studies have indicated that METTL3-mediated N6-methyladenosine (m6A) modification is closely associated with PC progression and prognosis. However, its underlying regulatory mechanisms remain unclear. In this study, we found that METTL3 was upregulated in PC tissues and cells and was associated with malignant tumor progression and poor progression-free survival in PC. Linc00662 was screened as a m6A-enriched RNA that promoted tumor growth and metastasis in PC cells and mouse models and was associated with poor clinical prognosis. Four m6A motifs were identified in Linc00662, which maintained the stability of Linc00662 in an IGF2BP3-coupled manner and were closely associated with the pro-tumor properties of Linc00662 in vitro and in vivo. ITGA1 was identified as a downstream gene regulated by Linc00662. Linc00662 recruites GTF2B to activate the transcription of ITGA1 in a m6A-dependent manner and initiates the formation of focal adhesions through the ITGA1-FAK-Erk pathway, thereby promoting malignant behavior in PC cells. The FAK inhibitor-Y15 obviously repressed tumor progression in Linc00662-overexpressing PC cells in vitro and in vivo. This study proposes a novel regulatory mechanism of Linc00662 in oncogene activation in PC and indicates that Linc00662 and its downstream genes are potential targets for PC therapy.

Background: Numerous studies have revealed that the long non-coding RNA LINC00662 is irregularly expressed in various cancers, as well as is correlated with cancer development and progression. Nevertheless, the clinical value of LINC00662 remains controversial. Hence, we explored the correlation of LINC00662 with cancer prognosis through meta-analysis and bioinformatics analysis. Methods: From the beginning through 12 March 2022, we searched for correlational studies on Web of Science, Embase, PubMed and The Cochrane Library. We used pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) to determine the significance of studies on survival outcomes and clinicopathological aspects in human cancers. Additionally, the Gene Expression Profiling Interactive Analysis (GEPIA) database was employed to confirm our findings. Results: Our meta-analysis of 14 studies comprising a total of 960 cancer patients revealed that LINC00662 overexpression was correlated with poor overall survival (HR = 1.91, 95% CI 1.49-2.45, p < 0.001) in cancer patients and relapse-free survival (HR = 2.12, 95% CI 1.19-3.76, p = 0.010) in hepatocellular carcinoma patients. The correlation between LINC00662 and OS was further supported by the results of subgroup analyses according to cancer type, follow-up time, HR availability, and NOS score. In addition, LINC00662 overexpression predicted advanced tumor stage (OR = 4.23, 95% CI 2.50-7.17, p < 0.001), larger tumor size (OR = 1.49, 95% CI 1.11-1.99, p = 0.008), earlier lymph node metastasis (OR = 2.40, 95% CI 1.25-4.59, p = 0.008), and earlier distant metastasis (OR = 4.78, 95% CI 2.57-8.88, p < 0.001). However, there were no statistically significant differences in age (OR = 1.16, 95% CI 0.90-1.51, p = 0.246), gender (OR = 1.10, 95% CI 0.79-1.53, p = 0.578), or differentiation grade (OR = 1.53, 95% CI 0.71-3.33, p = 0.280). Conclusion: LINC00662 expression upregulation is associated with poor prognosis and advanced clinicopathological features in patients with multiple tumors. LINC00662 may serve as a biomarker for the diagnosis and treatment of patients with tumors.

Paired-like homeodomain transcription factor 1 (PITX1) is frequently downregulated in cancers, including osteosarcoma (OS). However, its role in OS remains unknown. Therefore, we aimed to explore the functions and potential mechanisms of PITX1 in OS malignant progression. Elevated PITX1 suppressed OS cell proliferation and migration, based on transwell, proliferation, and colony formation assays. Pathway enrichment analysis of differentially-expressed genes between PITX1-overexpressing and control OS cells indicated that PITX1 expression was associated with the FAK/Src and PI3k/Akt signaling pathways. Mechanistically, ubiquitination assays and rescue experiments showed that PITX1 interacted with transcription factor STAT3, leading to decreased STAT3 transcriptional activity, which repressed the expression of LINC00662. Specific knockdown of LINC00662 reduced the tumor growth and invasion of OS cells induced by downregulated PITX1. Moreover, exosomal LINC00662, derived from PITX1 knockdown OS cell lines activated M2 macrophages in cell co-culture assays. M2 macrophage secreted several cytokines, among which CCL22 was found to cause OS cell EMT. Collectively, our data indicate that PITX1 suppresses OS cell proliferation and metastasis by downregulating LINC00662. Moreover, LINC00662 can be packaged into OS cell-derived exosomes to mediate M2 macrophage polarization to promote OS metastasis via CCL22.

OBJECTIVE: The angiogenesis is among the primary factors that affect tumor recurrence and distant organ metastasis in colorectal cancer (CRC). N6-methyladenosine (m6A) modification is one of the most common chemical modifications in eukaryotic mRNA, especially at the post-transcriptional level. Methyltransferase-like 3 (METTL3) promoting angiogenesis in a variety of tumors has been reported. However, the mechanism of how METTL3 dual-regulates the stability of long non-coding RNAs (lncRNAs) and vascular-related factor RNAs to affect angiogenesis in CRC is unclear.
METHODS: 64 paired CRC and adjacent normal tissues were collected. In vitro, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), actinomycin assay, methylated RNA immunoprecipitation (MeRIP) experiment,3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and colony formation assay were performed. The functions were also studied in zebrafish model animals in vivo.
RESULTS: We found that the vascular endothelial growth factor A(VEGFA), METTL3 and LINC00662 RNAs were highly expressed in CRC, and that METTL3 was significantly positively correlated with LINC00662 and VEGFA. The protein expression levels of CD31, CD34, VEGFA, m6A and METTL3 were all significantly increased in the CRC tissues. The angiogenesis experiments both in vivo and in vitro found that METTL3 and LINC00662 promoted angiogenesis in CRC. The actinomycin assay indicated that METTL3 maintained the stability of LINC00662 and VEGFA RNAs. In addition, the MeRIP experiment confirmed that the LINC00662 and VEGFA RNAs had METTL3-enriched sites.
CONCLUSIONS: These findings suggest that METTL3 and LINC00662 may both serve as diagnostic and prognostic predictive biomarkers for CRC and potential targets for anti-vascular therapy.

BACKGROUND: Breast cancer (BC) is one of the most prevalent malignancies among women globally. Emerging evidence indicates that long non-coding RNAs (lncRNAs) are associated with BC carcinogenesis. In the current study, we explored the mechanism by which LINC00662 regulates BC.
METHODS: Quantitative real-time PCR (qRT-PCR) assessed RNA expressions while western blot for protein levels. Kaplan Meier analysis evaluated overall survival (OS). Cytoplasmic/nuclear fractionation, RNA binding protein immunoprecipitation (RIP) and luciferase reporter assays probed into the underlying molecular mechanism of LINC00662 in BC. Xenograft model was established to explore the influence of LINC00662 on BC progression in vivo. R square graphs were utilized to represent RNA relationships.
RESULTS: LINC00662 is overtly overexpressed in BC tissues and cell lines. LINC00662 knockdown hampers cell proliferation, migration, invasion and stemness. LINC00662 expression is negatively correlated with OS of BC patients. LINC00662 up-regulates SOX2 expression by competitively binding to miR-144-3p, thereby modulating BC cell progression. Xenograft experiments verified that LINC00662 promotes BC tumor growth and cell stemness in vivo.
CONCLUSIONS: LINC00662 enhances cell proliferation, migration, invasion and stemness in BC by targeting miR-144-3p/SOX2 axis. The findings in the present study suggested that LINC00662 could be a potential therapeutic target for BC treatment.

Objective: LINC00662 is oncogenic in some human cancers, but no much was revealed concerning to its specific action in tumor angiogenesis. Given that, our study investigated the role of LINC00662 from esophageal squamous cell carcinoma (ESCC) cells-derived extracellular vehicles (EVs) in angiogenesis through microRNA (miR)-195-5p/vascular endothelial growth factor A (VEGFA) axis. Methods: Clinical tissue samples were collected from patients with ESCC, in which LINC00662, miR-195-5p and VEGFA expression was analyzed. ESCC cells were transfected, from which EVs were isolated. Human umbilical vein endothelial cells (HUVECs) were co-cultured with the pretreated EVs. After that, viability, colony formation ability, invasion, migration and tube formation ability of HUVECs were observed. Tumor xenograft in nude mice was performed to detect the effect of LINC00662, miR-195-5p or EV specific inhibitor GW4869 on tumor development. Results: LINC00662 and VEGFA were upregulated while miR-195-5p was downregulated in the cancer tissue of patients with ESCC. EVs derived from ESCC cells promoted viability, colony formation ability, invasion and tube formation ability of HUVECs. Downregulation of LINC00662 or upregulation of miR-195-5p reversed the promotion of EVs derived from ESCC cells on the viability, colony formation ability, invasion and tube formation ability of HUVECs in vitro and in vivo. VEGFA overexpression reversed EVs carrying restored miR-195-5p induced effects on HUVECs in vitro. Conclusion: In summary, elevated LINC00662 transferred by ESCC cells-derived EVs induces angiogenesis through downregulating miR-195-5p and upregulating VEGFA.

Recently, studies have shown that lncRNAs play important roles in regulation of cancer cells proliferation, apoptosis and metastasis. Here, through systematic bioinformatics analysis and screening, we identified a long noncoding RNA LINC00662 with high copy number amplification in NSCLC. High expression of LINC00662 predicted a poorer survival. The exact sequence full-length of LINC00662 was determined by rapid amplification of cDNA ends (RACE). We also found that LINC00662 could regulate lung cancer cell proliferation both in vitro and in vivo. Mechanically, we obtained global expression profile that respond to LINC00662 knockdown through RNA-Seq analysis. And we found that LINC00662 could bind to EZH2 and recruit EZH2 to the promoter regions of BIK, regulating the level of H3K27me3 in the BIK promoter, thus epigenetically repressing BIK expression. Our results shown that lncRNA LINC00662, driven by copy number amplification, promotes tumorigenesis by EZH2/BIK cell axis, indicating that it was a potential molecular target of NSCLC.