Genetic variants in several long noncoding RNA genes have been implicated in the occurrence and development of colorectal cancer (CRC). In this study, we explored the association between HAND2-AS1 gene rs2276941 polymorphism and the risk and clinical stage of CRC. A direct sequencing method was used to detect the rs2276941 polymorphism in 576 CRC patients and 864 healthy individuals. Real-time quantitative PCR technology was used to explore the expression of HAND2-AS1 and hsa-miR-1275 in colorectal tissues with different rs2276941 genotypes. Dual-luciferase reporter assay was used to assess the function of the rs2276941 polymorphism. We found that the rs2276941 polymorphism was associated with a decreased risk of CRC (TT vs. CC, OR = 0.38, 95% CI = 0.16–0.89, p = 0.03; TT vs. [CC+CT], OR = 0.40, 95% CI = 0.17–0.94, p = 0.03). Furthermore, a significant negative correlation was observed between the expression of HAND2-AS1 and hsa-miR-1275 in colorectal tissues with rs2276941 TT genotype. Functional experimental results showed that the rs2276941 T allele might promote the binding of HAND2-AS1 to hsa-miR-1275. The current study results suggested that HAND2-AS1 gene rs2276941 polymorphism affecting the binding of hsa-miR-1275 was associated with CRC risk and might serve as a CRC susceptibility biomarker.
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References
1.
ChenM.Y., FanK., ZhaoL.J., WeiJ.M., GaoJ.X., and LiZ.F. (2021). Long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) sponges microRNA-124-3p to up-regulate phosphodiesterase 4B (PDE4B) to accelerate the progression of Parkinson's disease. Bioengineered, 12, 708–719.
2.
GaoT., DaiX., JiangY., HeX., YuanS., and ZhaoP. (2020). LncRNA HAND2-AS1 inhibits proliferation and promotes apoptosis of non-small cell lung cancer cells by inactivating PI3K/Akt pathway. Biosci Rep 40,BSR20201870.
3.
GaoX., ZhangS., and ZhuZ. (2015). Lysyl oxidase rs1800449 polymorphism and cancer risk among Asians: evidence from a meta-analysis and a case-control study of colorectal cancer. Mol Genet Genomics, 290, 23–28.
4.
Ghafouri-FardS., HussenB.M., GharebaghiA., EghtedarianR., and TaheriM. (2021). LncRNA signature in colorectal cancer. Pathol Res Pract 222,153432.
5.
GongJ., FanH., DengJ., and ZhangQ. (2020). LncRNA HAND2-AS1 represses cervical cancer progression by interaction with transcription factor E2F4 at the promoter of C16orf74. J Cell Mol Med, 24, 6015–6027.
6.
GongJ., LiuW., ZhangJ., MiaoX., and GuoA.Y. (2015). lncRNASNP: a database of SNPs in lncRNAs and their potential functions in human and mouse. Nucleic Acids Res, 43, D181–D186.
7.
GruberA.R., LorenzR., BernhartS.H., NeuböckR., and HofackerI.L. (2008). The Vienna RNA websuite. Nucleic Acids Res, 36, W70–W74.
8.
GuX., ZhengQ., ChuQ., and ZhuH. (2021). HAND2-AS1: a functional cancer-related long non-coding RNA. Biomed Pharmacother 137,111317.
9.
HeJ., YuL., WangC.M., and ZhouX.F. (2018). MiR-1275 promotes non-small cell lung cancer cell proliferation and metastasis by regulating LZTS3 expression. Eur Rev Med Pharmacol Sci, 22, 2680–2687.
10.
HuangJ., ZhuL., ZhaoX., WuX., YangJ., XuB., et al. (2021). LncRNA SERPINB9P1 expression and polymorphisms are associated with ischemic stroke in a Chinese Han population. Neurol Sci, 43, 1143–1154.
11.
JiangN., ZouC., ZhuY., LuoY., ChenL., LeiY., et al. (2020a). HIF-1ɑ-regulated miR-1275 maintains stem cell-like phenotypes and promotes the progression of LUAD by simultaneously activating Wnt/β-catenin and Notch signaling. Theranostics, 10, 2553–2570.
12.
JiangZ., LiL., HouZ., LiuW., WangH., ZhouT., et al. (2020b). LncRNA HAND2-AS1 inhibits 5-fluorouracil resistance by modulating miR-20a/PDCD4 axis in colorectal cancer. Cell Signal 66,109483.
13.
KeumN., and GiovannucciE. (2019). Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol, 16, 713–732.
14.
LiuM.D., WuH., WangS., PangP., JinS., SunC.F., et al. (2018). MiR-1275 promotes cell migration, invasion and proliferation in squamous cell carcinoma of head and neck via up-regulating IGF-1R and CCR7. Gene, 646, 1–7.
15.
LiY., JingF., DingY., HeQ., ZhongY., and FanC. (2018). Long noncoding RNA CCAT1 polymorphisms are associated with the risk of colorectal cancer. Cancer Genet, 222, 13–19.
16.
RenH., LiZ., TangZ., LiJ., and LangX. (2020). Long noncoding MAGI2-AS3 promotes colorectal cancer progression through regulating miR-3163/TMEM106B axis. J Cell Physiol, 235, 4824–4833.
17.
ShangA., WangW., GuC., ChenW., LuW., SunZ., et al. (2020). Long non-coding RNA CCAT1 promotes colorectal cancer progression by regulating miR-181a-5p expression. Aging (Albany NY), 12, 8301–8320.
18.
Van NguyenS., ShamounL., LanderholmK., AnderssonR.E., WagsaterD., and DimbergJ. (2021). Cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene polymorphism (rs3087243) is related to risk and survival in patients with colorectal cancer. In Vivo, 35, 969–975.
19.
WangY., and CaiX. (2020). Long noncoding RNA HAND2-AS1 restrains proliferation and metastasis of breast cancer cells through sponging miR-1275 and promoting SOX7. Cancer Biomark, 27, 85–94.
20.
XiY., and XuP. (2021). Global colorectal cancer burden in 2020 and projections to 2040. Transl Oncol 14,101174.
21.
XingL., TangX., WuK., HuangX., YiY., and HuanJ. (2020). LncRNA HAND2-AS1 suppressed the growth of triple negative breast cancer via reducing secretion of MSCs derived exosomal miR-106a-5p. Aging (Albany NY), 13, 424–436.
22.
XuZ., LvH., WangY., HuC., ChenS., DuY., et al. (2020). HAND2-AS1 inhibits gastric adenocarcinoma cells proliferation and aerobic glycolysis via miRNAs sponge. Cancer Manag Res, 12, 3053–3068.
23.
YangJ.R., ShiM.X., and ZengY. (2019). LncRNA HAND2-AS1 inhibits proliferation and promotes apoptosis of chronic myeloid leukemia cells by sponging with micRNA-1275. Eur Rev Med Pharmacol Sci, 23, 2103–2111.
24.
YangX., WuS., LiX., YinY., and ChenR. (2020). MAGI2-AS3 rs7783388 polymorphism contributes to colorectal cancer risk through altering the binding affinity of the transcription factor GR to the MAGI2-AS3 promoter. J Clin Lab Anal 34,e23431.
25.
YangY., ChenL., GuJ., ZhangH., YuanJ., LianQ., et al. (2017). Recurrently deregulated lncRNAs in hepatocellular carcinoma. Nat Commun 8,14421.
26.
ZhaoD.M., DiaoY.E., and XuQ. (2020). Association of MDM4 gene rs4245739 polymorphism with the risk and clinical characteristics of colorectal cancer in a Chinese Han population. Pharmgenomics Pers Med, 13, 673–678.
27.
ZhouJ., LinJ., ZhangH., ZhuF., and XieR. (2018). LncRNA HAND2-AS1 sponging miR-1275 suppresses colorectal cancer progression by upregulating KLF14. Biochem Biophys Res Commun, 503, 1848–1853.
28.
ZhuX., JiangS., WuZ., LiuT., ZhangW., WuL., et al. (2021). Long non-coding RNA TTN antisense RNA 1 facilitates hepatocellular carcinoma progression via regulating miR-139-5p/SPOCK1 axis. Bioengineered, 12, 578–588.
