Department of Internal Medicine, Chenglong Campus Hospital, Sichuan Normal University, Sichuan Province China.
Department of Infectious Diseases, First Affiliated Hospital of Xinjiang Medical University, Xinjiang China.
Bioengineered. 2021 Dec;12(1):7964-7974. doi: 10.1080/21655979.2021.1984005.
Long non-coding RNAs (lncRNAs) play important regulatory roles in hepatocellular carcinoma (HCC). However, the function of LOC107985656 in HCC progression remains unclear. The lncRNA, mRNA and miRNA levels in HCC tissues or cells were measured using real-time quantitative polymerase chain reaction (RT-qPCR). The proliferation of cancer cells was evaluated using 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) viability and colony formation assays. Bioinformatics prediction, dual luciferase assay and RNA pull-down assay were performed to analyze the relationships between LOC107985656 and miR-106b-5p, or miR-106b-5p and large tumor suppressor 1 (LATS1). The protein expression levels were detected using Western blot. Results showed that LncRNA LOC107985656 was downregulated in HCC tissues and cells. Upregulation of LOC107985656 inhibited the proliferation of HCC cells, whereas its knockdown promoted this phenomenon. LOC107985656 could activate the tumor-suppressive Hippo pathway by repressing yes association protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, also known as TAZ) (two homologs of Yki) protein expression in HCC. Further investigation suggested that LOC107985656 regulated the expression of LATS1 by acting as a sponge for absorbing miR-106b-5p in HCC cells. In conclusion, this study unraveled the role of LOC107985656 following a ceRNA (competing endogenous RNAs) mechanism for the miR-106b-5p/LATS1 axis in HCC. The results indicate potential diagnostic and therapeutic applications of LOC107985656 in HCC.HCC: hepatocellular carcinoma; LncRNA: long non-coding RNA; LATS1: large tumor suppressor 1; MTT: 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide; YAP: yes association protein; WWTR1: WW domain-containing transcription regulator protein 1; cDNA: single-stranded complementary DNA; RT-qPCR: real-time quantitative polymerase chain reaction; Radio-Immunoprecipitation Assay (RIPA); BCA: bicinchoninic acid; ASO: antisense oligonucleotide; MST1/2: Ste20-like kinases 1/2; TEAD: TEA domain transcription factor; ceRNA: competing endogenous RNAs.
长链非编码 RNA（lncRNA）在肝细胞癌（HCC）中发挥重要的调控作用。然而，LOC107985656 在 HCC 进展中的功能尚不清楚。采用实时定量聚合酶链反应（RT-qPCR）检测 HCC 组织或细胞中的 lncRNA、mRNA 和 miRNA 水平。通过 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四唑溴盐（MTT）活力和集落形成实验评估癌细胞的增殖。采用生物信息学预测、双荧光素酶报告基因检测和 RNA 下拉实验分析 LOC107985656 与 miR-106b-5p 或 miR-106b-5p 与大肿瘤抑制因子 1（LATS1）之间的关系。采用 Western blot 检测蛋白表达水平。结果显示，lncRNA LOC107985656 在 HCC 组织和细胞中下调。LOC107985656 的上调抑制 HCC 细胞的增殖，而其下调则促进该现象。LOC107985656 通过抑制 HCC 细胞中 yes 相关蛋白（YAP）和 WW 结构域包含转录调节剂蛋白 1（WWTR1，也称为 TAZ）（Yki 的两个同源物）蛋白表达，激活肿瘤抑制性 Hippo 通路。进一步研究表明，LOC107985656 通过作为 HCC 细胞中 miR-106b-5p 的海绵吸附物来调节 LATS1 的表达。总之，本研究揭示了 LOC107985656 通过 ceRNA（竞争内源性 RNA）机制调节 HCC 中 miR-106b-5p/LATS1 轴的作用。这些结果表明 LOC107985656 具有 HCC 的潜在诊断和治疗应用。HCC：肝细胞癌；LncRNA：长链非编码 RNA；LATS1：大肿瘤抑制因子 1；MTT：3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四唑溴盐；YAP：yes 相关蛋白；WWTR1：WW 结构域包含转录调节剂蛋白 1；cDNA：单链互补 DNA；RT-qPCR：实时定量聚合酶链反应；放射性免疫沉淀法（RIPA）；BCA：双缩脲法；ASO：反义寡核苷酸；MST1/2：Ste20 样激酶 1/2；TEAD：TEA 结构域转录因子；ceRNA：竞争内源性 RNA。
