Long noncoding RNAs act as crucial regulators in plenty of human cancers, yet their potential roles and molecular mechanisms in chemoresistance are poorly understood. This study showed that a novel lncRNA, long intergenic noncoding RNA 152 (Linc00152 ), promoted tumor progression and conferred resistance to oxaliplatin (L-OHP)-induced apoptosis in vitro and in vivo. It antagonized chemosensitivity through acting as a competing endogenous RNA to modulate the expression of miR-193a-3p, and then erb-b2 receptor tyrosine kinase 4 (ERBB4). Knockdown of ERBB4 in colon cancer cells decreased AKT phosphorylation, which resulted in decreased L-OHP resistance. Consistent with above findings, the specific AKT signaling inhibitor and activator were used, respectively, which demonstrated that Linc00152 contributed to L-OHP resistance at least partly through activating AKT pathway. Further studies indicated that Linc00152 was increased and appeared to be an independent prognostic factor for decreased survival and increased disease recurrence in stage II and III colon cancer patients undergoing L-OHP-based chemotherapy after surgery. Collectively, our findings established Linc00152 as a candidate prognostic indicator of outcome and drug responsiveness in colon cancer patients, and the involvement of competing endogenous RNAs mechanism in Linc00152/ miR-193a-3p/ERBB4/AKT signaling axis may provide a novel choice in the investigation of drug resistance.
Expression microarrays are widely used for investigating the candidate molecular targets in human cancer. While genome-wide expression signatures screened by gene set enrichment analysis (GSEA) were not performed in Chinese gastric cancer (GC). To gain new molecular targets for GC, GSEA analysis was performed. In the present study, GSEA were used to pick out differentially expressed gene sets of our database. Total RNA of paired tissue samples (n = 48) and a tissue microarray containing 132 paired tissues were used to further validate expression levels of INHBA and its correction with clinicopathological factors. Upregulated INHBA expression in gastric cancer was screened and further confirmed by qPCR and immunostaining analysis. Increased INHBA expression was significantly correlated with the diameter of cancer and depth of tumor invasion. Patients with higher expression levels of INHBA had a shorter disease-free survival rate. It was effective to gain new molecular targets for GC by GSEA analysis. INHBA may be a poor survival indicator of GC.
Abstract. Colon cancer is one of the most frequently diagnosed cancer and the third most fatal malignancy worldwide. HOTAIR, a cancer-associated long non-coding RNA (lncRNA), is a powerful biomarker of metastasis and poor prognosis in a diverse group of cancers. Nevertheless, an understanding of how HOTAIR is involved in colon cancer progression is limited. In the present study, we hypothesized that HOTAIR plays a crucial role in colon cancer development. We evaluated the expression of HOTAIR in 120 colon cancer samples, matched adjacent non-tumor mucosa and 32 lymph node metastasis tissues by real-time PCR. Increased HOTAIR expression was significantly correlated with the depth of tumor invasion, lymph node metastasis, organ metastasis, histological differentiation, vascular invasion and advanced tumor stage. Patients with high HOTAIR expression had higher recurrence rates and reduced metastasis-free and overall survival than patients with low HOTAIR expression. Moreover, our findings revealed that HOTAIR had a limited effect on cell proliferation but significantly promoted colon cancer cell migration and invasion in vitro. Depletion of HOTAIR increased the expression of E-cadherin while concomitantly decreasing expression of vimentin and MMP9. Hence, HOTAIR may be another pleiotropic modulator participating in epithelial-mesenchymal transition (EMT). These results indicate that HOTAIR may also be a valuable predictor for colon cancer management; furthermore, this lncRNA may be a potential target for cancer prevention and treatment.
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