LncRNA MIR155HG Overexpression Promotes Proliferation, Migration, and Chemoresistance in Gastric Cancer Cells.

Long non-coding RNAs are thought to play a vital role in a variety of human malignancies. Studies have shown that MIR155 host gene (MIR155HG) acts as an oncogene in several cancers, but the function and its mechanism of MIR155HG in gastric cancer (GC) is still poorly understood. In this study, we determined the biological functions and underlying mechanisms of MIR155HG in GC cells. We found that expression levels of MIR155HG was increased markedly in GC patients' serum. In vitro and in vivo studies demonstrated that MIR155HG modulated the malignant phenotype of GC cells, such as cell proliferation, colony forming ability, cell migration ability, and tumor growth in nude mice. Next, our results revealed that NF-κB and STAT3 signaling pathways could be involved in regulating the malignant behavior of GC cells. Our rescue experiments showed that inhibiting NF-κB and STAT3 signaling pathways attenuated the phenotypes caused by MIR155HG overexpression. Moreover, cytotoxicity and apoptosis assays revealed overexpression of MIR155HG reduced the apotosis of GC cells induced by cisplatin and 5-FU. Together, our studies suggested that MIR155HG overexpression promoted proliferation, migration, and chemoresistance of GC cells. These results might provide a lncRNA-based target for GC treatment in future.

Knockdown of UBQLN1 Functions as a Strategy to Inhibit CRC Progression through the ERK-c-Myc Pathway.

PURPOSE: Colorectal cancer (CRC) is characterized by the absence of obvious symptoms in the early stage. Due to the high rate of late diagnosis of CRC patients, the mortality rate of CRC is higher than that of other malignant tumors. Accumulating evidence has demonstrated that UBQLN1 plays an important role in many biological processes. However, the role of UBQLN1 in CRC progression is still elusive. METHODS AND RESULTS: we found that UBQLN1 was significantly highly expressed in CRC tissues compared with normal tissues. Enhanced/reduced UBQLN1 promoted/inhibited CRC cell proliferation, colony formation, epithelial-mesenchymal transition (EMT) in vitro, and knockdown of UBQLN1 inhibited CRC cells' tumorigenesis and metastasis in nude mice in vivo. Moreover, the knockdown of UBQLN1 reduced the expression of c-Myc by downregulating the ERK-MAPK pathway. Furthermore, the elevation of c-Myc in UBQLN1-deficient cells rescued proliferation caused by UBQLN1 silencing. CONCLUSIONS: Knockdown of UBQLN1 inhibits the progression of CRC through the ERK-c-Myc pathway, which provides new insights into the mechanism of CRC progression. UBQLN1 may be a potential prognostic biomarker and therapeutic target of CRC.

Solute Carrier Family 27 Member 6 (SLC27A6) Possibly Promotes the Proliferation of Papillary Thyroid Cancer by Regulating c-MYC.

To investigate the expression and mechanism of LSC27A6 in papillary thyroid cancer (PTC). We analyzed the differential expression of SLC27A6 in PTC tissues and normal tissues based on the TCGA database and validated it using immunohistochemistry. Wilcoxon rank sum, chi-square test, or Fisher exact exam were used to analyze the relationship between the expression of SLC27A6 and clinicopathological information. Samples were divided into two groups according to whether BRAF was mutated or not, and Wilcoxon rank sum was used to determine whether the expression of SLC27A6 was related to BRAF mutation. The effects of SLC27A6 on the proliferation, migration, and apoptosis of PTC cells were detected by cell counting kit-8 (CCK8), colony formation assay, transwell assay, and flow cytometry. Spearman correlation analysis was used to evaluate the relationship between SLC27A6 and c-MYC. Protein expression was detected by Western blot. The expression of SLC27A6 was higher in PTC and positively correlated with N stage. SLC27A6 expression was higher in samples with BRAF mutations. Down-regulation of SLC27A6 inhibited cell proliferation, migration, and invasion and induced apoptosis. Spearman correlation analysis showed that SLC27A6 was positively correlated with c-MYC. Knockdown of SLC27A6 inhibited c-MYC expression. Our results suggest that SLC27A6 is overexpressed in PTC tissues and affects the progression of PTC by regulating c-MYC.

Overexpression of LINC00673 Promotes the Proliferation of Cervical Cancer Cells.

OBJECTIVE: To study the expression of LINC00673 in cervical cancer and cervical intraepithelial neoplasia (CIN) and to explore the role of LINC00673 in the development of cervical cancer. METHODS: The expression of LINC00673 in serum from cervical cancer patients, CIN patients, and healthy participants was detected by RT-qPCR. The function of LINC00673 in cervical cancer cells was analyzed using in vitro and in vivo experiments. RESULTS: Our results revealed that serum LINC00673 levels were highest in cervical cancer patients, followed by patients with CIN and healthy controls. In vitro experiments demonstrated that overexpression of LINC00673 enhanced the proliferation and cell cycle progression of HeLa and SiHa cells. In vivo experiments showed that the tumor weight and volume of nude mice subcutaneously injected with LINC00673-overexpressing HeLa cells were larger than those of nude mice injected with control cells (P < 0.05). Western blotting showed that cell cycle-related proteins cyclin A2 and cyclin E and interstitial-associated proteins Snail and N-cadherin were upregulated and p53 signaling pathway-related proteins were downregulated in LINC00673-overexpressing HeLa and SiHa cells. CONCLUSION: LINC00673 plays an important role in the development of cervical cancer and may serve as a new therapeutic target for cervical cancer.

Stabilization of oncogenic transcripts by the IGF2BP3/ELAVL1 complex promotes tumorigenicity in colorectal cancer.

The expression of RNA-binding proteins (RBPs) is dysregulated in colorectal cancer (CRC) and in other types of cancer. Among the RBPs, the insulin-like growth factor-2 messenger RNA binding protein (IGF2BP1-3) family is involved in the development of the colon and the progression of CRC. However, the regulation of mRNA fate by IGF2BP3 in CRC remains less well understood. Here, we show that IGF2BP3 interacts with ELAVL1 to coregulate a cohort of genes involved in the cell cycle and cell proliferation. Mechanistically, recognition of these mRNAs by the IGF2BP3/ELAVL1 complex leads to prolonged half-lives of the mRNA molecules and increased expression of the target genes, thereby driving CRC cell proliferation. Interestingly, knockdown of either IGF2BP3 or ELAVL1 impairs the IGF2BP3/ELAVL1 complex-enhanced mRNA stability, suggesting a functional interdependency between IGF2BP3 and ELAVL1 in CRC. Our findings reveal the molecular mechanism by which IGF2BP3 regulates mRNA stability and identify the cooperativity of the IGF2BP3/ELAVL1 complex as a novel therapeutic target in CRC.

α-enolase promotes tumorigenesis and metastasis via regulating AMPK/mTOR pathway in colorectal cancer.

The α-enolase (ENO1) plays pivotal roles in several types of cancer, but its clinical significance, functional role, and possible mechanism in colorectal cancer (CRC) have remained unclear. Expression level of ENO1 in CRC tissues was examined by qRT-PCR, Western blot, and immunohistochemistry. The effects of ENO1 on cell growth were investigated by MTT, colony formation, flow cytometry assays, and in vivo tumorigenic capacity analysis. The impacts of ENO1 on cell migration and invasion were also explored by scratch-healing, Transwell or Matrigel chamber assays, and in vivo metastatic capacity analysis. Our results showed that the expression level of ENO1 was significantly elevated in CRC tissues. High expression level of ENO1 was associated with disease progression in CRC patients. Overexpression of ENO1 in HCT116 cell line promoted cell proliferation, migration, and invasion in vitro as well as tumorigenesis and metastasis in vivo. In other hand, ablation of ENO1 in HCT116 cells led to totally reverse effects. Mechanistically, we revealed ENO1 could regulate AMPK/mTOR signaling pathway. AMPK pathway activation or mTOR pathway suppression blocked these ENO1 induced alterations. Together, our results demonstrated that ENO1 is a potent promoter of CRC genesis and metastasis at least in part though regulating AMPK/mTOR pathway. These findings also suggested that ENO1 may be a promising therapeutic target in CRC patients.