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Background Increasing investigations indicate that long noncoding RNA (lncRNA) is responsible for diverse biological functions during the progression of cancer. However, its functions and underlying mechanisms remain elusive. Here, we investigated the MAFG-AS1- expression profile in esophageal squamous-cell carcinoma (ESCC) patients and explored its biological function and potential molecular mechanisms. Methods qRT-PCR and the GEPIA data base were used to evaluate expression levels of MAFG-AS1 in ESCC tissue and cells. WST1-proliferation, -migration, and -invasion assays were performed to define the role of MAFG-AS1 in ESCC. Potential molecular mechanisms of MAFG-AS1 were investigated with online bioinformatic analysis, qRT-PCR, and rescue assays. Results MAFG-AS1 was upregulated in 45 ESCC-tissue samples and cell lines compared to that of adjacent nontumor tissue and normal esophageal cells. Higher MAFG-AS1 expressionindicated poor survival. Gain- and loss-of-function experiments suggested that MAFG-AS1 promoted ESCC-cell proliferation, migration, and invasion. Molecular mechanism analysis and rescue assay showed that miR143 inhibitors partly abolished the suppression of MAFG-AS1 knockdown on EC109-cells proliferation. Moreover, we found that LASP1 specifically targeted miR143. Collectively, these data indicated that MAFG-AS1 served as a ceRNA to elevate LASP1 levels by sponging miR143, and played an oncogenic role in ESCC. Conclusion Our research findings demonstrate that MAFG-AS1 is a key regulator through a novel MAFG-AS1-miR143-LASP1 axis in ESCC development and progression, which may offer a potential therapeutic target for ESCC.

Accumulating evidence has uncovered long non-coding RNAs (lncRNAs) as central regulators in the pathogenesis of diverse human cancers including colorectal cancer (CRC). The present study discovered that a novel lncRNA ITIH4 antisense RNA 1 (ITHI4-AS1) was frequently under-expressed in most normal human tissues, including colon tissues. Therefore, we aimed to investigate the role of ITHI4-AS1 in CRC. Interestingly, a significant overexpression of ITIH4-AS1 was observed in CRC cell lines relative to normal NCM460 cells. Also, we investigated the facilitating role of ITIH4-AS1 in CRC cell growth and metastasis both in vitro and in vivo. Additionally, we explained that ITIH4-AS1 upregulation in CRC was attributed to downregulation or even depletion of RE1 silencing transcription factor (REST), a presently identified transcriptional repressor for ITIH4-AS1. Meanwhile, the contribution of ITIH4-AS1 to CRC development was validated to rely on the activation of the JAK/STAT3 pathway. More importantly, we verified that FUS interacted with both ITIH4-AS1 and STAT3, and that ITIH4-AS1 evoked nuclear translocation of phosphorylated (p)-STAT3 in CRC through recruiting FUS. In summary, our findings unveiled for the first time that REST downregulation-enhanced ITIH4-AS1 exerts pro-tumor functions in CRC through FUS-dependent activation of the JAK/STAT3 pathway, implying that targeting ITIH4-AS1 may be a novel effective strategy for CRC therapy. Keywords: ITIH4-AS1, colorectal cancer, REST, FUS, STAT3

Background: Long noncoding RNAs (lncRNAs), a class of noncoding RNA nucleotides >200 bp, has been demonstrated to play vital role in the development of cancer. FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) has been reported as an lncRNA which acts as a tumor-promoting effect in some cancers. However, the role of it in esophageal squamous cell carcinoma (ESCC) and its potential regulatory mechanism was unclear now. Methods: qRT-PCR was used to detect the levels of FEZF1-AS1 and mRNA CTNNB1 (β-catenin) in ESCC tissues and cells. Cell transfection experiments were used to knock down or overexpress the level of FEZF1-AS1 in EC1 and EC9706 cell lines. WST-1 assays, cell cycle assays, scratch wound assays, migration, and invasion assays were used to evaluate the function of FEZF1-AS1 in ESCC progression. Results: FEZF1-AS1 was remarkably upregulated in ESCC tissues and cell lines. Silencing of FEZF1-AS1 significantly inhibited the migration and invasion of ESCC cells, while overexpression of FEZF1-AS1 notably accelerated ESCC migration and invasion. Meanwhile, the levels of FEZF1-AS1 had no effect on ESCC cell proliferation and cell cycle. We also found that β-catenin was upregulated in ESCC tissues, and the level of it was positively correlated with the expression of FEZF1-AS1. Silencing of FEZF1-AS1 could decrease the mRNA and protein level of β-catenin, while overexpression FEZF1-AS1 could lead to the contrary. Conclusion: Our results suggested that the expression of lncRNA FEZF1-AS1 played an important role in ESCC progression, especially the motility of the tumor. FEZF1-AS1 may provide us with a new sight for ESCC treatment.

Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) function as essential regulators in the development and progression of multiple tumors. However, the molecular mechanisms of MIR31HG in regulating ESCC progression remain unknown. Here, we confirmed that MIR31HG facilitated ESCC cells proliferation in vivo. Besides, MIR31HG knockdown increases the percentage of cells at the G1 phase, along with reduced arrest in S phase and MIR31HG overexpression exhibits the opposite effects. Overexpressed MIR31HG decreases the percentage of apoptotic ESCC cells. Interestingly, MIR31HG can function as a competing endogenous RNA by sponging miR-34a. The rescue experiments demonstrated that MIR31HG function is partially reversed by inhibiting miR-34a. In addition, we found c-Met is a target gene of miR-34a and is indirectly regulated by MIR31HG. Taken together, our findings revealed that MIR31HG promotes ESCC progression by regulating miR-34a/ c-Met axis and may provide a new prospective for exploration and understanding of the biological effects of esophageal squamous cell carcinoma.

Exosomes derived from human umbilical cord mesenchymal stem cells (HUCMSCs) expressing microRNAs (miRs) have been highlighted as important carriers for gene or drug therapy. Hence, this study aimed to explore the role of exosomal miR-148b-3p from HUCMSCs in breast cancer. Clinical samples subjected to RT-qPCR detection revealed that miR-148b-3p was poorly expressed, while tripartite motif 59 (TRIM59) was highly expressed in breast cancer tissues. Online analyses available at miRanda, TargetScan, and miRbase databases revealed that miR-148b-3p could bind to TRIM59, while dual-luciferase reporter gene assay further verified that TRIM59 was a target gene of miR-148b-3p. Next, miR-148b-3p mimic or inhibitor and siRNA against TRIM59 were delivered into the breast cancer cells (MDA-MB-231) to alter the expression of miR-148b-3p and TRIM59 so as to evaluate their respective effects on breast cancer cellular processes. Evidence was obtained demonstrating that miR-148b-3p inhibited cell proliferation, invasion, and migration, but promoted cell apoptosis in breast cancer by down-regulating TRIM59. Next, MDA-MB-231 cells were co-cultured with the exosomes derived from HUCMSCs expressing miR-148b-3p. The results of co-culture experiments demonstrated that HUCMSCs-derived exosomes carrying miR-148b-3p exerted inhibitory effects on MDA-MB-231 progression in vitro. In vivo experimentation further confirmed the anti-tumor effects of HUCMSCs-derived exosomes carrying miR-148b-3p. Taken together, HUCMSC-derived exosomes carrying miR-148b-3p might suppress breast cancer progression, which highlights the potential of exosomes containing miR-148b-3p as a promising therapeutic approach for breast cancer treatment.

Increasing evidence has demonstrated that histone deacetylase 2 (HDAC2) participates in the regulation of a variety of biological processes in numerous tumors. However, the potential role of HDAC2 in the development and progression of esophageal squamous cell carcinoma (ESCC) remains elusive. Immunohistochemistry was utilized to detect the expression of HDAC2, Cell Counting Kit-8 was used to determine the cell proliferation, and flow cytometry was employed to investigate cell cycle and cell apoptosis. Finally, western blotting was employed to detect the protein expression of cyclin D1, p21, B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax). The present study found that expression of HDAC2 protein in ESCC tissues was significantly increased compared with atypical hyperplasia tissues and normal esophageal mucosa (P0.05), but was closely associated with the histological grade, invasion depth, tumor-node-metastasis stage and lymph node metastasis, respectively (all P

AIMS：: Recent research showed that Long non-protein coding RNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) plays a crucial role in the course of tumor formation. The present study was aimed to explore its role in esophageal squamous cell carcinoma (ESCC).Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to examine the expression levels of FTH1P3, mRNA SP1 and NF-kB in ESCC samples and cell lines. The impact of FTH1P3 knockdown was evaluated by WST-1 assays, colony formation assays, scratch wound assays, migration and invasion assays.FTH1P3 was significantly upregulated in ESCC tissues and cells (P 0.001). Knockdown of FTH1P3 notably decreased the proliferation, migration, and invasion capacity of ESCC cells. Silencing of FTH1P3 decreased the expression of specificity protein 1 (Sp1) and NF-kB (p65) in EC9706 and EC1.FTH1P3 plays a crucial role in ESCC tumorigenesis, and can be used as a potential therapeutic target for ESCC.

Background/Aims: The Hippo-Yap pathway is associated with tumor development and progression. However, little evidence is available concerning its role in cancer cell apoptosis and migration via mitochondrial homeostasis. Here, we identify mitochondrial fission as a regulator of the Hippo–Yap pathway in human rectal cancer tumorigenesis and metastasis. Methods: In this study, we performed loss-of function assays concerning Yap in RCC via shRNA. Cellular viability and apoptosis were measured via MTT, the TUNEL assay and trypan blue staining. Mitochondrial function was assessed via JC1 staining, the mPTP opening assay, mitochondrial respiratory function analysis, electron microscopy and immunofluorescence analysis of HtrA2/Omi. Mitophagy and mitochondrial fission were assessed via western blots and immunofluorescence. Cell migration was evaluated via the Transwell assay, wound-healing assay and immunofluorescence analysis of F-actin. The interaction between JNK and Yap was detected via co-immunoprecipitation and Yap recombinant mutagenic plasmid transfection. Western blots were used to analyze signaling pathways in conjunction with JNK inhibitors or HtrA2/Omi siRNA. Results: Yap is upregulated in human rectal cancer cells, where its expression correlates positively with cell survival and migration. Functional studies established that silencing of Yap drove JNK phosphorylation, which induced Drp1 activation and translocation to the surface of mitochondria, initiating mitochondrial fission. Excessive mitochondrial fission mediated HtrA2/Omi leakage from the mitochondria into the cytoplasm, where HtrA2/Omi triggered cellular apoptosis via the mitochondrial apoptosis pathway. Moreover, released HtrA2/Omi also phosphorylated cofilin and inhibited cofilin-mediated F-actin polymerization. F-actin collapse perturbed lamellipodia formation and therefore impaired cellular migration and invasion. Conclusion: Collectively, our results demonstrate that Hippo-Yap can serve as a tumor promoter in human rectal cancer and acts by restricting JNK/Drp1/mitochondrial fission/ HtrA2/Omi, with potential implications for new approaches to human rectal cancer therapy.

Background Long non-coding RNAs (lncRNAs) are powerful factors influencing the tumorigenesis and metastasis of multiple carcinomas. LncRNA MNX1-AS1 plays critical roles in the progression of tumor formation according to recent research, while its roles in esophageal squamous cell carcinoma (ESCC) remains unknown. Methods The expression levels of lncRNA MNX1-AS1 were examined in ESCC tissues by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The role of lncRNA MNX1-AS1 was performed by WST-1 proliferation assays, migration and invasion assays. Besides, the molecular mechanism of lncRNA MNX1-AS1 was verified by online bioinformatics, qRT-PCR and rescue assays. Results MNX1-AS1 was signifcantly upregulated in ESCC tissues. It was conformed that high MNX1-AS1 expression was associated with ESCC lymph node metastasis. Moreover, we found that knockdown of MNX1-AS1 apparently suppressed the cell proliferation, migration, and invasion capacity. Flow cytometry analysis showed MNX1-AS1 regulated ESCC cell cycle and apoptosis progression. Mechanism analysis revealed that miR-34a inhibitor could rescue the influence of inhibiting MNX1-AS1 on ESCC cells migration by serving as competing endogenous RNA (ceRNAs). Furthermore, we found that miR-34a specifically targeted SIRTI. Conclusions Taken together, we demonstrated that lncRNA MNX1-AS1/miR-34a/SIRT1 regulatory axis could play an important role in ESCC progression, and MNX1-AS1 may act as a novel potential biomarker for esophageal squamous cell carcinoma.