Leng Fei, Miu Yan-Yu, Zhang Yi, Luo Hao, Lu Xiao-Li, Cheng Hui, Zheng Zhi-Guo
The Affiliated Stomatological Hospital of Nanchang University, The Key Laboratory of Oral Biomedicine, Nanchang, Jiangxi 330006, P.R. China.
Oncol Lett. 2021 Oct;22(4):697. doi: 10.3892/ol.2021.12958. Epub 2021 Aug 2.
HOXB-AS3 is a long non-coding RNA and recent studies have shown that the HOXB-AS3-encoded micro-peptide was associated with the progression of colon cancer tumorigenesis; however, the biofunction of HOXB-AS3 varies in different types of cancer and the potential function in oral squamous cell carcinoma (OSCC) is still unknown. The Cancer Genome Atlas (TCGA) database was searched and the expression patterns of HOXB-AS3 in head and neck carcinoma were analyzed. Reverse transcription-quantitative PCR and western blot analysis was used to measure the mRNA and protein expression level of HOXB-AS3 in patients with OSCC, respectively. Next, HOXB-AS3 was knocked down in 2 OSCC cell lines to investigate the biological function of the HOXB-AS3-encoded protein using a Cell Counting Kit-8 and colony formation assays. To further identify the potential mechanism of the HOXB-AS3-encoded protein, co-immunoprecipitation was also used to detect the interaction between HOXB-AS3 and IGF2BP2, while HOXB-AS3 was re-expressed to determine whether the HOXB-AS3-encoded protein and not HOXB-AS3 exerted its function in OSCC. HOXB-AS3 was upregulated in OSCC tissues, in both TCGA database and in patients with OSCC recruited into the present study. HOXB-AS3 was associated with poor prognosis in OSCC. The proliferation and viability decreased in the 2 OSCC cell lines following knock down of HOXB-AS3. HOXB-AS3 was also found to encode a protein that directly interacted with IGF2BP2 and thereby promoted the stability of c-myc. Taken together, the results from the present study indicated that increased HOXB-AS3 expression was associated with poor prognosis in OSCC. This indicated that HOXB-AS3 and its encoded protein promoted OSCC cell proliferation and viability by maintaining c-Myc mRNA stability by directly binding to IGF2BP2.
HOXB-AS3是一种长链非编码RNA，最近的研究表明，HOXB-AS3编码的微肽与结肠癌肿瘤发生的进展有关；然而，HOXB-AS3的生物功能在不同类型的癌症中有所不同，其在口腔鳞状细胞癌（OSCC）中的潜在功能仍然未知。检索癌症基因组图谱（TCGA）数据库并分析HOXB-AS3在头颈癌中的表达模式。分别采用逆转录定量PCR和蛋白质免疫印迹分析来检测OSCC患者中HOXB-AS3的mRNA和蛋白质表达水平。接下来，在2种OSCC细胞系中敲低HOXB-AS3，使用细胞计数试剂盒-8和集落形成试验来研究HOXB-AS3编码蛋白的生物学功能。为了进一步确定HOXB-AS3编码蛋白的潜在机制，还采用免疫共沉淀法检测HOXB-AS3与IGF2BP2之间的相互作用，同时重新表达HOXB-AS3以确定是HOXB-AS3编码的蛋白而非HOXB-AS3在OSCC中发挥作用。在TCGA数据库以及本研究纳入的OSCC患者中，HOXB-AS3在OSCC组织中均上调。HOXB-AS3与OSCC的不良预后相关。敲低HOXB-AS3后，2种OSCC细胞系的增殖和活力均下降。还发现HOXB-AS3编码一种直接与IGF2BP2相互作用的蛋白，从而促进c-myc的稳定性。综上所述，本研究结果表明HOXB-AS3表达增加与OSCC的不良预后相关。这表明HOXB-AS3及其编码蛋白通过直接结合IGF2BP2维持c-Myc mRNA稳定性，从而促进OSCC细胞增殖和活力。
