Role of long non-coding RNA HULC in cell proliferation, apoptosis and tumor metastasis of gastric cancer: A clinical and in vitro investigation

Abstract

Long non-coding RNAs (lncRNAs) are emerging as key molecules in human cancer. Highly upregulated in liver cancer (HULC), an lncRNA, has recently been revealed to be involved in hepatocellular carcinoma development and progression. It remains unclear, however, whether HULC plays an oncogenic role in human gastric cancer (GC). In the present study, we demonstrated that HULC was significantly overexpressed in GC cell lines and GC tissues compared with normal controls, and this overexpression was correlated with lymph node metastasis, distant metastasis and advanced tumor node metastasis stages. In addition, a receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic values and the area under the ROC curve of HULC was up to 0.769. To uncover its functional importance, gain- and loss-of-function studies were performed to evaluate the effect of HULC on cell proliferation, apoptosis and invasion in vitro. Overexpression of HULC promoted proliferation and invasion and inhibited cell apoptosis in SGC7901 cells, while knockdown of HULC in SGC7901 cells showed the opposite effect. Mechanistically, we discovered that overexpression of HULC could induce patterns of autophagy in SGC7901 cells; more importantly, autophagy inhibition increased overexpression of HULC cell apoptosis. We also determined that silencing of HULC effectively reversed the epithelial-to-mesenchymal transition (EMT) phenotype. In summary, our results suggest that HULC may play an important role in the growth and tumorigenesis of human GC, which provides us with a new biomarker in GC and perhaps a potential target for GC prevention, diagnosis and therapeutic treatment.

Loss of α-Tubulin Acetylation Is Associated with TGF-β-induced Epithelial-Mesenchymal Transition

“…Recent studies have shown that microRNAs in the miR-200 family, miR-101 and miR-506 are markedly downregulated during EMT and also strong regulators of EMT through regulating transcription factors involved in EMT (22)(23)(24). Similarly, several lncRNAs are found to induce EMT, including HULC, MALAT-1, H19, and HOTAIR (25)(26)(27)(28). These genes and RNAs are often recognized as markers for EMT.…”

The role of long noncoding RNAs in cancer metastasis

“…Lung Upregulated [190] Suppression of E-cadherin [191] Bladder Upregulated [192] Breast Upregulated [193] Pancreatic Upregulated [194] MEG3 Meningioma Downregulated [195] Regulation of autophagy [196] and DNA repair [197] Lung Downregulated [198] Gastric Downregulated [199] HOTAIR Liver Upregulated [200] Reprogramming of chromatin state [201,202] Breast Upregulated [203] Pancreatic Upregulated [204] GAS5 Liver Downregulated [205] Controls invasion by control of miRNAs [205,206] Gastric Downregulated [207] Breast Downregulated [208] H19 Liver Upregulated [209] Chromatin remodeling [210] and TGF-β regulation [211] Pancreatic Upregulated [137,212] Gastric Upregulated [213] HULC Liver Upregulated [147] Regulates tumor microenvironment interactions [214] Gastric Upregulated [148] Breast Upregulated [92,146] SPRY4-IT1 Melanoma Upregulated [139] Proliferation and invasion via regulation of EZH2 [143] Lung Upregulated [215] SCC Upregulated [142] and LBR to initiate transcriptional silencing [77] . Taken together, it is crucial that these biochemistry-focused studies continue, such that, novel therapies can be developed to modulate a specific biological activity mediated by a particular lncRNA of interest.…”

“…Two recent studies suggest that HULC promotes angiogenesis as well as neo-angiogenesis, essential processes in the progression of metastasis as micro-metastatic lesions require an oxygen-rich environment to meet the demand of tumor growth within an hypoxic environment. For instance, Zhao et al [148] found that overexpression of HULC in hepatocellular cancer cells results in an increase in the pro-angiogenic factor SPHK1. Specifically, HULC functions by sequestering miR-107, a bona fide target of which is the TF E2F1.…”

New Developments of Gastric Cancer Biomarker Research

“…However, recent research suggested some serum non-coding RNA could also be potential gastric specific markers. Long non-coding RNA HULC and H19 were reported to be promising novel biomarkers in plasma of patients with gastric cancer [70][71][72][73][74][75]. MicroRNA is a relatively stable species of RNA in the serum.…”