Li Jia, Wang Xinjing, Lu Wenli, Xiao Yuan, Yu Yi, Wang Xinqiong, Xu Chundi, Shen Baiyong
Department of Paediatrics, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghai, China.
Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghai, China.
Am J Transl Res. 2018 Mar 15;10(3):1022-1035. eCollection 2018.
Hypoxia commonly occurs in solid cancers, especially in gastric cancer due to its rapid growth. The ability of gastric cancer cells to survive and progress under hypoxic conditions has been known for decades, but the mechanisms underlying this characteristic remain poorly understood. As cancer cells undergo changes in their genetic profile under certain conditions, we investigated the expression profile of non-coding RNAs (circRNAs, lncRNAs, and miRNAs) and mRNAs in gastric cancer MKN-28 cells under hypoxic conditions via sequencing and subsequent bioinformatic analyses. In addition, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the results. We identified a number of significantly differentially expressed circRNAs, lncRNAs, miRNAs, and mRNAs in hypoxia-exposed MKN-28 cells relative to the normoxia control, and results of qRT-PCR were consistent with sequencing data. Pathway enrichment analyses revealed the principal functions of the significantly deregulated genes. Furthermore, examination of co-expression and competing endogenous RNA (ceRNAs) networks illustrated the complex regulatory pathways among non-coding RNAs and mRNAs, implicating these pathways in gastric cancer. In conclusion, our findings provide a novel perspective on non-coding RNAs and mRNAs and lay the foundation for future research on the potential roles of non-coding RNAs in gastric cancer under hypoxic conditions.
缺氧在实体癌中普遍存在，尤其是在胃癌中，因为其生长迅速。几十年来，人们已经知道胃癌细胞在缺氧条件下存活和进展的能力，但这种特性背后的机制仍知之甚少。由于癌细胞在某些条件下其基因谱会发生变化，我们通过测序及后续生物信息学分析，研究了缺氧条件下胃癌MKN-28细胞中非编码RNA（环状RNA、长链非编码RNA和微小RNA）和信使RNA的表达谱。此外，还使用定量逆转录聚合酶链反应（qRT-PCR）来验证结果。我们发现，与常氧对照组相比，缺氧处理的MKN-28细胞中有许多显著差异表达的环状RNA、长链非编码RNA、微小RNA和信使RNA，qRT-PCR结果与测序数据一致。通路富集分析揭示了显著失调基因的主要功能。此外，对共表达和竞争性内源RNA（ceRNA）网络的研究阐明了非编码RNA和信使RNA之间复杂的调控途径，表明这些途径与胃癌有关。总之，我们的研究结果为非编码RNA和信使RNA提供了新的视角，并为未来研究非编码RNA在缺氧条件下胃癌中的潜在作用奠定了基础。
