lncRNA TTN-AS1调控miR-107/HMGA1信号轴影响乳腺癌细胞放射敏感性的研究

doi:10.3760/cma.j.cn113030-20220808-00266

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摘要目的探究长链非编码RNA（lncRNA） TTN-AS1对乳腺癌细胞放射敏感性的影响及机制。方法用实时反转录PCR（qRT-PCR）检测TTN-AS1在各乳腺癌细胞中的表达。将MDA-MB-231细胞分为0 Gy组、4 Gy组、阴性对照（NC）+4 Gy组、si-TTN-AS1+4 Gy组、si-TTN-AS1+miR-107抑制剂+4 Gy组、si-TTN-AS1+miR-107抑制剂+si-HMGA1+4 Gy组。用CCK-8法和流式细胞术检测各组细胞增殖和凋亡率。结果相较于乳腺上皮细胞,TTN-AS1在乳腺癌细胞株中显著高表达（P<0.001）。相比于NC+4 Gy组,si-TTN-AS1+4 Gy组细胞增殖能力均显著降低（P<0.05）,细胞凋亡显著增加（P<0.001）。相比于0 Gy组,4 Gy组细胞TTN-AS1和HMGA1在放疗8 h至24 h表达均显著增加（P值均<0.01）,miR-107在放疗8 h至24 h表达均显下调（P<0.001）。si-TTN-AS1+miR-107抑制剂+4 Gy组细胞增殖能力均显著高于si-TTN-AS1+4 Gy组（P<0.001）,细胞凋亡显著低于si-TTN-AS1+4 Gy组（P<0.001）。相比于si-TTN-AS1+miR-107抑制剂+4 Gy组,si-TTN-AS1+miR-107抑制剂+si-HMGA1+4 Gy组细胞增殖能力均显著降低（P<0.001）,细胞凋亡显著增加（P<0.001）。结论 TTN-AS1可促进乳腺癌细胞的放射敏感性,其机制为调控miR-107/HMGA1信号轴。

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	茅芯慧
	王珍
	张建庆
	朱成斌

关键词 ：乳腺肿瘤, TTN-AS1, 放射敏感性

Abstract：Objective To investigate the effect and mechanism of long non-coding RNA (lncRNA) TTN-AS1 on the radiosensitivity of breast cancer cells. Methods The expression of TTN-AS1 in breast cancer cells was detected by real-time reverse transcription PCR (qRT-PCR). MDA-MB-231 cells were divided into the 0 Gy group, 4 Gy group, negative control (NC) +4 Gy group, si-TTN-AS1+4 Gy group, si-TTN-AS1+miR-107 inhibitor+4 Gy group, and si-TTN-AS1+miR-107 inhibitor+si-HMGA1+4 Gy group. CCK-8 assay and flow cytometry were used to detect the proliferation and apoptosis rates in each group. Results Compared with breast epithelial cells, TTN-AS1 was significantly highly expressed in breast cancer cell lines (P<0.001). Compared with the NC+4 Gy group, the cell proliferation ability was significantly decreased (P<0.05) and cell apoptosis was significantly increased (P<0.001) in the si-TTN-AS1+4 Gy group. Compared with the 0 Gy group, the expression levels of TTN-AS1 and HMGA1 from 8 h to 24 h after radiotherapy were significantly up-regulated (both P<0.01), whereas the expression of miR-107 was significantly down-regulated from 8 h to 24 h after radiotherapy in the 4 Gy group (P<0.001). The cell proliferation ability in the si-TTN-AS1+miR-107 inhibitor+4 Gy group was significantly higher than that in the si-TTN-AS1+4 Gy group (P<0.001), and cell apoptosis was significantly lower than that in the si-TTN-AS1+4 Gy group (P<0.001). Compared with the si-TTN-AS1+miR-107 inhibitor+4 Gy group, cell proliferation ability was significantly decreased (P<0.001), whereas cell apoptosis was significantly increased in the si-TTN-AS1+miR-107 inhibitor+si-HMGA1+4 Gy group (P<0.001). Conclusion TTN-AS1 can promote the radiosensitivity of breast cancer cells by regulating the miR-107/HMGA1 signaling axis.

Key words： Breast neoplasms TTN-AS1 Radiosensitivity

收稿日期: 2022-08-08

基金资助:新疆维吾尔自治区自然科学基金（2022D01C642）

通讯作者: 朱成斌,Email：1464381784@qq.com

引用本文:

茅芯慧,王珍,张建庆等. lncRNA TTN-AS1调控miR-107/HMGA1信号轴影响乳腺癌细胞放射敏感性的研究[J]. 中华放射肿瘤学杂志, 2023, 32(5): 451-456.

Mao Xinhui,Wang Zhen,Zhang Jianqing et al. LncRNA TTN-AS1 affects the radiosensitivity of breast cancer cells by regulating miR-107/HMGA1 signaling axis[J]. Chinese Journal of Radiation Oncology, 2023, 32(5): 451-456.

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http://journal12.magtechjournal.com/Jweb_fszlx/CN/10.3760/cma.j.cn113030-20220808-00266 或 http://journal12.magtechjournal.com/Jweb_fszlx/CN/Y2023/V32/I5/451

[1] Katsura C, Ogunmwonyi I, Kankam HK, et al.Breast cancer: presentation, investigation and management[J]. Br J Hosp Med (Lond), 2022,83(2):1-7. DOI: 10.12968/hmed.2021.0459.
[2] To NH, Nguyen HQ, Thiolat A, et al.Radiation therapy for triple-negative breast cancer: emerging role of microRNAs as biomarkers and radiosensitivity modifiers. A systematic review[J]. Breast Cancer Res Treat, 2022,193(2):265-279. DOI: 10.1007/s10549-022-06533-3.
[3] Casey DL, Gupta GP, Ollila DW.The role of intraoperative radiation in early-stage breast cancer[J]. Clin Breast Cancer, 2021,21(2):103-111. DOI: 10.1016/j.clbc.2020.12.007.
[4] He J, Zhu S, Liang X, et al.LncRNA as a multifunctional regulator in cancer multi-drug resistance[J]. Mol Biol Rep, 2021,48(8):1-15. DOI: 10.1007/s11033-021-06603-7.
[5] Smolarz B, Zadrożna-Nowak A, Romanowicz H. The role of lncRNA in the development of tumors, including breast cancer[J]. Int J Mol Sci, 2021,22(16): 8427-8440. DOI: 10.3390/ijms22168427.
[6] Zuo Z, Ji S, He L, et al.LncRNA TTN-AS1/miR-134-5p/PAK3 axis regulates the radiosensitivity of human large intestine cancer cells through the P21 pathway and AKT/GSK-3β/β-catenin pathway[J]. Cell Biol Int, 2020,44(11):2284-2292. DOI: 10.1002/cbin.11436.
[7] Fang J, Huang C, Ke J, et al. lncRNA TTN-AS1 facilitates proliferation, invasion,epithelial-mesenchymal transition of breast cancer cells by regulating miR-139-5p/ZEB1 axis[J]. J Cell Biochem, 2020, 121(12): 4772-4784. DOI: 10.1002/jcb.29700.
[8] Katsura C, Ogunmwonyi I, Kankam HK, et al.Breast cancer: presentation, investigation and management[J]. Br J Hosp Med (Lond), 2022,83(2):1-7. DOI: 10.12968/hmed.2021.0459.
[9] Lai Y, Chen Y, Lin Y, et al.Down-regulation of lncRNA CCAT1 enhances radiosensitivity via regulating miR-148b in breast cancer[J]. Cell Biol Int, 2018,42(2):227-236. DOI: 10.1002/cbin.10890.
[10] Liu L, Zhu Y, Liu AM, et al.Long noncoding RNA LINC00511 involves in breast cancer recurrence and radioresistance by regulating STXBP4 expression via miR-185[J]. Eur Rev Med Pharmacol Sci, 2019,23(17):7457-7468. DOI: 10.26355/eurrev_201909_18855.
[11] Shen L, Wu Y, Li A, et al.LncRNA TTN‑AS1 promotes endometrial cancer by sponging miR‑376a‑3p[J]. Oncol Rep, 2020,44(4):1343-1354. DOI: 10.3892/or.2020.7691.
[12] Fu D, Lu C, Qu X, et al.LncRNA TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the miR-134-5p/MBTD1 axis[J]. Aging (Albany NY), 2019,11(19):8374-8385. DOI: 10.18632/aging.102325.
[13] Qiu P, Dou Y, Ma LZ, et al.Long non-coding RNA TTN-AS1 promotes the metastasis in breast cancer by epigenetically activating DGCR8[J]. Eur Rev Med Pharmacol Sci, 2020,24(14):7559. DOI: 10.26355/eurrev_202007_22212.
[14] Xue J, Zhang Z, Li X, et al.Long non-coding RNA TTN-AS1 promotes breast cancer cell migration and invasion via sponging miR-140-5p[J]. Oncol Lett, 2020,20(5):157-168. DOI: 10.3892/ol.2020.12018.
[15] Feng H, Wang Q, Xiao W, et al.LncRNA TTN-AS1 regulates miR-524-5p and RRM2 to promote breast cancer progression[J]. Onco Targets Ther, 2020,13:4799-4811. DOI: 10.2147/OTT.S243482.
[16] Yip CW, Sivaraman DM, Prabhu AV, et al.Functional annotation of lncRNA in high-throughput screening[J]. Essays Biochem, 2021,65(4):761-773. DOI: 10.1042/EBC20200061.
[17] Wang G, Ma C, Shi X, et al.miR-107 Enhances the sensitivity of breast cancer cells to paclitaxel[J]. Open Med (Wars), 2019,14:456-466. DOI: 10.1515/med-2019-0049.
[18] Zhou J, Sun X, Zhang X, et al.miR-107 is involved in the regulation of NEDD9-mediated invasion and metastasis in breast cancer[J]. BMC Cancer, 2022,22(1):533. DOI: 10.1186/s12885-022-09603-3.
[19] Arancibia T, Morales-Pison S, Maldonado E, et al.Association between single-nucleotide polymorphisms in miRNA and breast cancer risk: an updated review[J]. Biol Res, 2021,54(1):26-44. DOI: 10.1186/s40659-021-00349-z.
[20] Zanin R, Pegoraro S, Ros G, et al.HMGA1 promotes breast cancer angiogenesis supporting the stability, nuclear localization and transcriptional activity of FOXM1[J]. J Exp Clin Cancer Res, 2019,38(1):313-335. DOI: 10.1186/s13046-019-1307-8.
[21] Song J, Cui D, Wang J, et al.Overexpression of HMGA1 confers radioresistance by transactivating RAD51 in cholangiocarcinoma[J]. Cell Death Discov, 2021,7(1):322-333. DOI: 10.1038/s41420-021-00721-8.