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Objectives To investigate the role of long noncoding RNA (lncRNA) nuclear‐enriched abundant transcript 1 (NEAT1) in regulating sorafenib (Sora) sensitivity of hepatocellular carcinoma (HCC) cells and possible signaling pathways. Methods HCC cell lines and tumor tissue were quantified for NEAT1 expression by quantitative polymerase chain reaction (qPCR). Following shRNA (short hairpin RNA) knockdown of NEAT1, cell viability, apoptosis, and related protein expression were measured after drug treatment. The downstream target of NEAT1, including miR‐335 and c‐Met was studied using a combination of luciferase binding assay, gene knockdown/overexpression, western blot analysis, and cell viability/apoptosis assay. Cancer cells with NEAT1 knockdown were transplanted onto nude mice for in vivo tumorigenesis assay. Results Silencing of NEAT1 in HCC cells facilitated Sora sensitivity by enhancing drug‐induced apoptosis, and led to smaller tumor size on nude mice. Mechanistic study suggested that miR‐335 was negatively regulated by NEAT1, and miR‐335 further suppressed c‐Met–Akt pathway, whose activation caused drug resistance of HCC cells. The knockdown of miR‐335, or overexpression of c‐Met, all remarkably abolished the proapoptotic effect of NEAT1 knockdown in HCC cells. Conclusion lncRNA NEAT1 mediates Sora resistance of HCC cells by suppressing miR‐335 expression, and disinhibition on c‐Met–Akt signaling pathway. Our results provide potency of NEAT1 as the biomarker for drug resistant HCC and possible treating targets.

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Background. MicroRNA (miRNA) dysregulation was commonly seen in papillary thyroid carcinoma (PTC), and miR-195 was verified to be downregulated in PTC by the large data set analysis from The Cancer Genome Atlas (TCGA). Our study aimed to explore the biological functions and the underlying molecular mechanisms of miR-195 in PTC. Methods. The relative expression of miR-195 and its target genes were assessed by quantitative RT-PCR assay in 38 pairs of PTC and the adjacent thyroid tissues. Assays were performed to evaluate the effect of miR-195 on the proliferation, migration, and invasion in PTC cell lines. Moreover, we searched for targets of miR-195 and explored the possible molecular pathway of miR-195 in PTC. Results. We found that miR-195 was downregulated in PTC cell lines and tissues. Overexpression of miR-195 significantly inhibited cell proliferation, migration, and invasion in K1 and BCPAP cell lines. CCND1 and FGF2, which had inverse correlations with miR-195 in clinical specimens, were found to be the direct targets of miR-195. Furthermore, miR-195 might be involved in PTC tumorigenesis by suppressing the Wnt/β-catenin signaling pathway. Conclusions. These results highlight an important role of miR-195 in the initiation and progression of PTC and implicate the potential application of miR-195 in PTC target therapy.

A B S T R A C TDecision making is the crucial step in many real applications such as organization management, financial planning, products evaluation and recommendation. Rational decision making is to select an alternative from a set of different ones which has the best utility (i.e., maximally satisfies given criteria, objectives, or preferences). In many cases, decision making is to order alternatives and select one or a few among the top of the ranking. Orderings provide a natural and effective way for representing indeterminate situations which are pervasive in commonsense reasoning. Ordering based decision making is then to find the suitable method for evaluating candidates or ranking alternatives based on provided ordinal information and criteria, and this in many cases is to rank alternatives based on qualitative ordering information. In this paper, we discuss the importance and research aspects of ordering based decision making, and review the existing ordering based decision making theories and methods providing future research directions.