LncRNA LINC00337 sponges mir-1285-3p to promote proliferation and metastasis of lung adenocarcinoma cells by upregulating YTHDF1.

BACKGROUND: Emerging studies have shown that long noncoding RNAs (lncRNAs) predominantly function in the carcinogenesis of multiple developing human tumors. The current study aimed to investigate the underlying mechanisms of LINC00337 in lung adenocarcinoma. METHODS: We analyzed TCGA and GTEx datasets and chose LINC00337 as the research object. Cell proliferation, cell apoptosis, cell cycle, migration, and invasion were detected in the gain and loss experiments of LINC00337 both in vitro and in vivo. Moreover, RNA pull-down, luciferase reporter assays, western blotting analysis, and rescue experiments were performed to investigate the underlying molecular mechanisms of LINC00337 function. RESULTS: LINC00337 expression was remarkably upregulated in lung adenocarcinoma. In addition, LINC00337 knockdown was shown to repress cell migration, invasion, and proliferation, as well as the cell cycle, and gear up apoptosis in lung adenocarcinoma in vitro and in vivo. With respect to the mechanism, LINC00337 knockdown boosted miR-1285-3p expression and then restrained YTHDF1 expression post-transcriptionally. Crucially, both miR-1285-3p decrement and YTHDF1 overexpression successfully reversed the influence on cell proliferation, migration, invasion, and apoptosis caused by LINC00337 shRNA. CONCLUSIONS: These results suggest that LINC00337 acts as an oncogenic lncRNA, targeting miR-1285-3p and regulating YTHDF1 expression, to promote the progression of lung adenocarcinoma.

Long non-coding RNA LINC00337 induces autophagy and chemoresistance to cisplatin in esophageal squamous cell carcinoma cells via upregulation of TPX2 by recruiting E2F4.

Esophageal cancer represents the eighth most frequently occurring cancer, as well as the sixth most widespread cause of cancer-related deaths. In recent years, accumulating evidence has implicated long non-coding RNAs in the progression of esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the potential involvement and underlying mechanisms of LINC00337 in ESCC. Expression patterns of LINC00337 and targeting protein for Xenopus kinesin-like protein 2 (TPX2) in ESCC tissues and cells were detected using RT-qPCR and immunohistochemical staining. Next, the interactions among LINC00337, E2F4, and TPX2 were identified using chromatin immunoprecipitation, dual-luciferase reporter, and RNA-binding protein immunoprecipitation assays, suggesting that LINC00337 could recruit E2F4 to enhance the transcription of TPX2. Thereafter, the regulatory roles of LINC00337 and TPX2 in ESCC were analyzed by altering the expression of LINC00337 or TPX2 in ESCC cells following treatment with cisplatin (DDP). The levels of autophagy-related proteins Beclin1 and LC3II/LC3I, viability, autophagy, apoptosis, and chemoresistance of ESCC cells to DDP were measured following transfection treatment with different plasmids. Additionally, the role of the LINC00337/E2F4/TPX2 axis was assessed in vivo by measuring tumor formation in nude mice. The results demonstrated that LINC00337 upregulated TPX2, consequently leading to elevated levels of Beclin1 and LC3II/LC3I, promoted cell viability and autophagy, while inhibiting apoptosis and chemosensitivity to DDP in ESCC. In sum, the current study evidenced that the overexpression of LINC00337 could potentially enhance ESCC cell autophagy and chemoresistance to DDP via the upregulation of TPX2 by recruiting E2F4. Thus, LINC00337 may serve as a potential candidate for the treatment of ESCC.

LINC00337 induces tumor development and chemoresistance to paclitaxel of breast cancer by recruiting M2 tumor-associated macrophages.

BACKGROUND: M2 tumor-associated macrophages are closely related to the progression and prognosis of breast cancer (BCa), and could be regulated by long intergenic non-coding RNAs (lincRNAs). Moreover, the differential expression of lincRNAs affects tumor resistance. This study focused on the potential involvement and mechanism of LINC00337 in BCa. METHODS: The expression of LINC00337 in BCa was detected by bioinformatics analysis and RT-qPCR. Cell viability and proliferation were analyzed by cell counting kit-8 (CCK-8) and clone formation assay. BCa cells were treated with different concentrations of paclitaxel (PAX) to determine the chemotherapy resistance of LINC00337. Tumor formation assay, Western blot, ELISA and immunohistochemistry were performed to determine the relationship between LINC00337 and PAX in vivo. Macrophages were induced to M2-like polarization, and then functional experiments (CCK-8, wound healing) and molecular experiments (ELISA, RT-qPCR, Western blot) were used to verify the role of LINC00337. RESULTS: LINC00337 was up-regulated in BCa. High-expressed LINC00337 accelerated viability and proliferation of BCa cells, improved the resistance of BCa cells to PAX, and accelerated tumor growth. Overexpressed LINC00337 up-regulated the expressions of M2 macrophage markers and M-CSF, and reduced the level of GM-CSF. PAX significantly reduced the viability of BCa cells and down-regulated LINC00337. Furthermore, the successfully induced M2 type macrophages to promote BCa cell activity, migration and EMT protein expression, and LINC00337 enhanced the effect of M2 type macrophages. ShLINC00337 had the opposite effect to overexpressed LINC00337. CONCLUSION: LINC00337 accelerated the malignant phenotype of BCa cells and promoted chemoresistance to paclitaxel through M2-like macrophages.

Long noncoding RNA Linc00337 functions as an E2F1 co-activator and promotes cell proliferation in pancreatic ductal adenocarcinoma.

BACKGROUND: Long noncoding RNA (lncRNA) Linc00337 has been implicated in lung, gastric, colorectal and esophageal squamous cell carcinoma progression via various mechanisms; however, its clinicopathological significance and role in pancreatic ductal adenocarcinoma (PDAC) progression remains largely unknown. METHODS: Multiple approaches such as bioinformatic analysis, Transfection, quantitative real-time-PCR, Western blotting, animal studies, RNA-immunoprecipitation (RIP), RNA-pulldown and RNA-Fluorescence in situ hybridization (RNA-FISH) and were utilized to explore the role of Linc00337 in PDAC. RESULTS: Here we identified Linc00337 is an oncogenic lncRNA during PDAC progression. We found that the expression of Linc00337 is elevated in PDAC tissues and the higher Linc00337 predicts dismal prognosis. Functionally, Linc00337 promotes PDAC cell proliferation and cell cycle transition both in vitro and in vivo. Mechanistically, Linc00337 binds to E2F1 and functions as an E2F1 coactivator to trigger the targets expression during PDAC progression. CONCLUSION: Our results demonstrate a reciprocal regulation mechanism between Linc00337 and E2F1 in PDAC progression and report the clinical value of Linc00337 for PDAC prognosis and treatment.

LINC00337 Regulates KLF5 and Maintains Stem-Cell Like Traits of Cervical Cancer Cells by Modulating miR-145.

Accumulating literature and evidence has highlighted the cancer stem-like cell (CSC) model as a cellular mechanism responsible for the phenotypic heterogeneity observed in various types of cancers, including cervical cancer. Long non-coding RNAs (lncRNAs) have been implicated in the retention of stem cell-like traits in cancer cells. However, the role of lncRNAs in the acquisition and maintenance of CSCs in cervical cancer remains largely unknown. Hence, the current study identified that LINC00337 knockdown diminished the CSC-like properties of CD44+/CD24low/-SFCs, evidenced by a decline in the generation of tumorospheres and colonies, a reduction in multi-drug resistance gene-1 (MDR-1), Nanog, Sox2, and Oct4 expression, along with an enhancement in cell apoptosis. RNA pull-down assays and RNA immunoprecipitation revealed the role of LINC00337 as a competing endogenous RNA (ceRNA) of microRNA-145 (miR-145). Furthermore, the miR-145 mRNA target, Kruppel-like factor 5 (KLF5), was decreased in CD44+/CD24low/-SFCs upon LINC00337 knockdown. The in vitro results were reproduced in in vivo studies, which provided verification attesting that LINC00337 knockdown attenuated the tumorigenicity of CD44+/CD24low/-SFCs in nude mice. Taken together, the key findings of the current study demonstrate that LINC00337 acts as an oncogenic lncRNA in cervical cancer and exerts its influence on the expression of KLF5 and the maintenance of cancer stem cell-like properties by means of downregulating miR-145.

Long noncoding RNA LINC00337 promote gastric cancer proliferation through repressing p21 mediated by EZH2.

Gastric cancer is one of the most common human malignancies. Some long noncoding RNA (lncRNA) has been validated to be oncogene in gastric cancer. In this research, we found that LINC00337 was up-regulated in the gastric cancer cells and tissue specimens. Clinically, the ectopic LINC00337 overexpression indicates the poor clinical outcome. The functional experiments illustrated that LINC00337 silencing repressed the proliferation, invasion and tumor growth in vitro and in vivo. The mechanical experiments showed that LINC00337 epigenetically repressed the p21 via EZH2-mediated inhibition. Overall, this finding suggests that LINC00337 acts as the oncogene to promote gastric cancer cells proliferation through epigenetically repressing p21 mediated by EZH2, providing a new insight for gastric cancer.

Long noncoding RNA LINC00337 accelerates the non-small-cell lung cancer progression through inhibiting TIMP2 by recruiting DNMT1.

Accumulating evidence reveals the essential roles of long noncoding RNAs (lncRNAs) in the non-small-cell lung cancer (NSCLC) tumorigenesis. Here, our research investigated the biological roles of novel lncRNA LINC00337 in the NSCLC tumorigenesis and discover the potential mechanism. In the NSCLC tissue and cell lines, LINC00337 was found to be remarkedly up-regulated, and the ectopic LINC00337 overexpression indicated the poor survival of NSCLC patients. In vitro, gain and loss of functional assays showed that LINC00337 promoted the progression of NSCLC cells, including proliferation and invasion. In vivo, LINC00337 knockdown inhibited the tumor growth of NSCLC cells. Mechanically, LINC00337 could recruit the epigenetic repressor DNMT1 to the promoter region of TIMP2 to silence its expression. In conclusion, our study found the critical regulation of lncRNA LINC00337 for the NSCLC through epigenetic regulation, which may serve as a predictive biomarker and potential therapeutic target.