Citation: | GUO Chenming, LUO Zhiwen, KONG Han, YANG Zhen, WANG Yiyang, Dilimulati·AISIMUTULA. Mechanism of LncRNA XIST regulating proliferation, migration, invasion and apoptosis of breast cancer cells through miR-20a-5p/HMGA2 axis[J]. Journal of Clinical Medicine in Practice, 2023, 27(5): 61-66, 71. DOI: 10.7619/jcmp.20222508 |
To investigate the effects and mechanisms of LncRNA XIST on proliferation, migration, invasion and apoptosis of breast cancer cells.
Normal mammary epithelial cells MCF-10A and breast cancer cell lines MCF-7, T47D and Bcap-37 cells were selected and transfected into MCF-7 and T47D cells with different substances. They were set as blank group (no transfection), si-XIST group (transfection si-XIST), si-NC group (transfection si-NC), microRNA-20a-5p group (transfection miR-20a-5p mimics) and miR-NC group (transfection miR-NC). CCK-8 was used to detect cell proliferation; Transwell was used to detect cell invasion ability; cell migration ability was detected by scratch test; apoptosis was detected by TUNEL staining. Luciferase reporter gene assay was used to verify the targeting relationships between LncRNA XIST and miR-20a-5p as well as between miR-20a-5p and high mobility group protein A2 (HMGA2). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of LncRNA XIST and miR-20a-5p. The expression level of HMGA2 was detected by Western blot.
Compared with MCF-10A cells, LncRNA XIST expression levels in MCF-7, T47D and Bcap-37 cells were significantly increased, while miR-20a-5p expression level was significantly decreased (P < 0.05). Down-regulating LncRNA XIST or up-regulating miR-20a-5p inhibited proliferation, invasion and migration of breast cancer cells, and promoted cell apoptosis (P < 0.05). LncRNA XIST negatively regulated miR-20a-5p, and miR-20a-5p negatively regulated HMGA2.
Down-regulated LncRNA XIST inhibits proliferation, migration andinvasion of breast cancer cells and promotes cell apoptosis through miR-20a-5p/HMGA2 axis.
[1] |
KATSURA C, OGUNMWONYI I, KANKAM H K, et al. Breast cancer: presentation, investigation and management[J]. Br J Hosp Med (Lond), 2022, 83(2): 1-7.
|
[2] |
WINKLE M, EL-DALY S M, FABBRI M, et al. Noncoding RNA therapeutics-challenges and potential solutions[J]. Nat Rev Drug Discov, 2021, 20(8): 629-651. doi: 10.1038/s41573-021-00219-z
|
[3] |
SMOLARZ B, ZADROZNA-NOWAK A, ROMANOWICZ H. The role of LncRNA in the development of tumors, including breast cancer[J]. Int J Mol Sci, 2021, 22(16): 8427. doi: 10.3390/ijms22168427
|
[4] |
LIU Y J, ZHANG P Y, WU Q Y, et al. Long non-coding RNA NR2F1-AS1 induces breast cancer lung metastatic dormancy by regulating NR2F1 and ΔNp63[J]. Nat Commun, 2021, 12(1): 5232. doi: 10.1038/s41467-021-25552-0
|
[5] |
张娜, 易茂林. LncRNA XIST通过海绵吸附miR-133a调控甲状腺癌细胞的增殖和凋亡[J]. 贵州医科大学学报, 2021, 46(8): 917-924. https://www.cnki.com.cn/Article/CJFDTOTAL-GYYB202108008.htm
|
[6] |
才昊, 韩亮, 李晓飞. LncRNA XIST通过调控miR-186-5p促进非小细胞肺癌的增殖和侵袭实验研究[J]. 陕西医学杂志, 2020, 49(7): 781-787, 803. doi: 10.3969/j.issn.1000-7377.2020.07.004
|
[7] |
YAN Z Z, LI J, GUO J, et al. LncRNA XIST sponges microRNA-448 to promote malignant behaviors of colorectal cancer cells via regulating GRHL2[J]. Funct Integr Genomics, 2022, 22(5): 977-988. doi: 10.1007/s10142-022-00873-5
|
[8] |
胡炜, 邵安静, 李春霞, 等. 沉默miR-20a-5p的肝癌细胞恶性生物学行为及Zbed3、Axin蛋白表达情况观察[J]. 山东医药, 2022, 62(11): 28-32. https://www.cnki.com.cn/Article/CJFDTOTAL-SDYY202211007.htm
|
[9] |
LI J, YE D L, SHEN P, et al. MiR-20a-5p induced WTX deficiency promotes gastric cancer progressions through regulating PI3K/AKT signaling pathway[J]. J Exp Clin Cancer Res, 2020, 39(1): 212. doi: 10.1186/s13046-020-01718-4
|
[10] |
XU J X, FANG X J, LONG L Y, et al. HMGA2 promotes breast cancer metastasis by modulating Hippo-YAP signaling pathway[J]. Cancer Biol Ther, 2021, 22(1): 5-11. doi: 10.1080/15384047.2020.1832429
|
[11] |
ZHAO W Y, GENG D H, LI S Q, et al. LncRNA HOTAIR influences cell growth, migration, invasion, and apoptosis via the miR-20a-5p/HMGA2 axis in breast cancer[J]. Cancer Med, 2018, 7(3): 842-855. doi: 10.1002/cam4.1353
|
[12] |
LI P, WANG L H, LI P F, et al. Silencing lncRNA XIST exhibits antiproliferative and proapoptotic effects on gastric cancer cells by up-regulating microRNA-132 and down-regulating PXN[J]. Aging (Albany NY), 2020, 13(10): 14469-14481.
|
[13] |
WANG H R, LI H M, YU Y K, et al. Long non-coding RNA XIST promotes the progression of esophageal squamous cell carcinoma through sponging miR-129-5p and upregulating CCND1 expression[J]. Cell Cycle, 2021, 20(1): 39-53. doi: 10.1080/15384101.2020.1856497
|
[14] |
ZHANG M, WANG F, XIANG Z, et al. LncRNA XIST promotes chemoresistance of breast cancer cells to doxorubicin by sponging miR-200c-3p to upregulate ANLN[J]. Clin Exp Pharmacol Physiol, 2020, 47(8): 1464-1472. doi: 10.1111/1440-1681.13307
|
[15] |
郭会, 方艳君, 李翠娥, 等. 过/降表达miR-20a-5p的骨肉瘤细胞增殖、侵袭能力及Bax、Bcl-2、E2F5蛋白表达观察[J]. 山东医药, 2022, 62(11): 42-46. https://www.cnki.com.cn/Article/CJFDTOTAL-SDYY202211010.htm
|
[16] |
HE Y, MA H, WANG J, et al. MiR-20a-5p inhibits endometrial cancer progression by targeting Janus kinase 1[J]. Oncol Lett, 2021, 21(5): 427. doi: 10.3892/ol.2021.12688
|
[17] |
YANG H B, CHEN Z, LIU Z M. MiR-20a-5p negatively regulates NR4A3 to promote metastasis in bladder cancer[J]. J Oncol, 2021, 2021: 1377989.
|
[18] |
BAI X D, HAN G H, LIU Y, et al. MiRNA-20a-5p promotes the growth of triple-negative breast cancer cells through targeting RUNX3[J]. Biomed Pharmacother, 2018, 103: 1482-1489. doi: 10.1016/j.biopha.2018.04.165
|
[19] |
李会芳, 侯永强, 王明军, 等. 乳腺癌组织FOXP3、HMGA2、RASAL2的表达及与临床病理特征和预后的关系[J]. 现代生物医学进展, 2021, 21(20): 3959-3964. https://www.cnki.com.cn/Article/CJFDTOTAL-SWCX202120032.htm
|
[20] |
李晨阳, 张学红. MiR-154靶向HMGA2基因在人子宫内膜癌中的表达及其对癌细胞恶性生物学行为的影响[J]. 兰州大学学报: 医学版, 2022, 48(1): 21-27. https://www.cnki.com.cn/Article/CJFDTOTAL-LZYX202201006.htm
|