The expression of miR-92a in breast cancer tissues and its effect on the migration and invasion behavior of breast cancer cells by targeting regulation of KLF4_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 ZHANG Lan , XU Yuan , ZHAO Bing , LI Juntao

Department of Breast Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450000, P. R. China;

Corresponding author：

ZHANG Lan, Email: 17162664764@163.com

Keywords：

breast cancer; microRNA-92a; kruppel-like factor 4

DOI：

10.7507/1007-9424.202105043

Video：

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Objective To investigate the expression of miR-92a in breast cancer tissues and whether it can influence the migration and invasion ability of breast cancer cells through kruppel-like factor 4 (KLF4). Methods ① The expressions of miR-92a and KLF4 mRNA in cancer tissues and adjacent tissues were detected by qRT-PCR in 122 breast cancer patients who were operated in our hospital from May 2017 to October 2019. ② The expression of miR-92a in MCF-7 breast cancer cells was up-regulated or knocked out. Cell survival rate was detected by MTT assay, cell migration ability was detected by scratch assay, cell invasion ability was detected by Transwell assay, and the relative expression levels of KLF4, E-cadherin (E-cad), and N-cadherin (N-cad) proteins were detected by Western blotting. ③ The targeting relationship between miR-92a and KLF4 was detected by dual luciferase reporter gene assay. Results ① The relative expression levels of miR-92a and KLF4 mRNA in cancer tissues were higher than those in adjacent tissues (P<0.05). ② The up-regulation of miR-92a expression had no effect on the survival rate of MCF-7 breast cancer cells, but the migration and invasion ability of cells were enhanced (P<0.05). The knockdown of miR-92a expression decreased the survival rate of MCF-7 breast cancer cells and the ability of cell migration and invasion (P<0.05). ③ The miR-92a and KLF4 had a direct targeting relationship, up-regulation of miR-92a expression increased the relative expression levels of KLF4 and N-cad proteins, while decreased the relative expression level of E-cad protein (P<0.05). After knockout of miR-92a expression, the relative expression levels of KLF4 and N-cad proteins were decreased, while the relative expression level of E-cad protein was increased (P<0.05). Conclusion The miR-92a is highly expressed in breast cancer cells, and knockout of miR-92a expression can inhibit KLF4 signaling pathway and reduce the migration and invasion ability of breast cancer cells.

Citation： ZHANG Lan, XU Yuan, ZHAO Bing, LI Juntao. The expression of miR-92a in breast cancer tissues and its effect on the migration and invasion behavior of breast cancer cells by targeting regulation of KLF4. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(2): 173-178. doi: 10.7507/1007-9424.202105043 Copy

1.	Ni D, Teng J, Cheng Y, et al. MicroRNA-92a promotes non-small cell lung cancer cell growth by targeting tumor suppressor gene FBXW7. Mol Med Rep, 2020, 22(4): 2817-2825.
2.	Mao QQ, Chen JJ, Xu WJ, et al. miR-92a-3p promotes the proliferation and invasion of gastric cancer cells by targeting KLF2. J Biol Regul Homeost Agents, 2020, 34(4): 1333-1341.
3.	Li X, Guo S, Min L, et al. miR-92a-3p promotes the proliferation, migration and invasion of esophageal squamous cell cancer by regulating PTEN. Int J Mol Med, 2019, 44(3): 973-981.
4.	Chen L, Shi J, Wu Y, et al. CircRNA CDR1as promotes hepatoblastoma proliferation and stemness by acting as a miR-7-5p sponge to upregulate KLF4 expression. Aging (Albany NY), 2020, 12(19): 19233-19253.
5.	Huang Z, Yan Y, Tang P, et al. TEAD4 as a prognostic marker promotes cell migration and invasion of urinary bladder cancer via EMT. Onco Targets Ther, 2021, 14: 937-949.
6.	席剑铭, 张能, 李晓光, 等. 过表达KLF4通过Wnt/β-catenin信号途径调控膀胱癌细胞上皮间质转化及迁移. 中国肿瘤生物治疗杂志, 2019, 26(8): 862-867.
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8.	Plum PS, Warnecke-Eberz U, Drebber U, et al. Upregulation of miR-17-92 cluster is associated with progression and lymph node metastasis in oesophageal adenocarcinoma. Sci Rep, 2019, 9(1): 12113. doi: 10.1038/s41598-019-48624-0.
9.	Sand M, Hessam S, Amur S, et al. Expression of oncogenic miR-17-92 and tumor suppressive miR-143-145 clusters in basal cell carcinoma and cutaneous squamous cell carcinoma. J Dermatol Sci, 2017, 86(2): 142-148.
10.	Li Y, Lauriola M, Kim D, et al. Adenomatous polyposis coli (APC) regulates miR17-92 cluster through β-catenin pathway in colorectal cancer. Oncogene, 2016, 35(35): 4558-4568.
11.	Yang C, Jia X, Zhou J, et al. The miR-17-92 gene cluster is a blood-based marker for cancer detection in non-small-cell lung cancer. Am J Med Sci, 2020, 360(3): 248-260.
12.	Lu X, Lu J, Wang S, et al. Circulating serum exosomal miR-92a-3p as a novel biomarker for early diagnosis of gastric cancer. Future Oncol, 2021, 17(8): 907-919.
13.	Peng Q, Shen Y, Lin K, et al. Identification of microRNA-92a and the related combination biomarkers as promising substrates in predicting risk, recurrence and poor survival of colorectal cancer. J Cancer, 2019, 10(14): 3154-3171.
14.	Yu H, Song H, Liu L, et al. MiR-92a modulates proliferation, apoptosis, migration, and invasion of osteosarcoma cell lines by targeting Dickkopf-related protein 3. Biosci Rep, 2019, 39(4): BSR20190410. doi: 10.1042/BSR20190410.
15.	Huang JH, Zhou QH, Chen CC, et al. MicroRNA miR-92a-3p regulates breast cancer cell proliferation and metastasis via regulating B-cell translocation gene 2 (BTG2). Bioengineered, 2021, 12(1): 2033-2044.
16.	Wu H, Li S. Long non-coding RNA MT1JP exerts anti-cancer effects in breast cancer cells by regulating miR-92-3p. Gen Physiol Biophys, 2020, 39(1): 59-67.
17.	Liu Z, Wu X, Tian Y, et al. Pylori infection induces CXCL8 expression and promotes gastric cancer progress through downregulating KLF4. Mol Carcinog, 2021, 60(8): 524-537.
18.	Cannizzaro E, Bannister AJ, Han N, et al. DDX3X RNA helicase affects breast cancer cell cycle progression by regulating expression of KLF4. FEBS Lett, 2018, 592(13): 2308-2322.
19.	Zhou H, Liu Y, Zhu R, et al. FBXO32 suppresses breast cancer tumorigenesis through targeting KLF4 to proteasomal degradation. Oncogene, 2017, 36(23): 3312-3321.
20.	Wang H, Hu X, Yang F, et al. miR-325-3p promotes the proliferation, invasion, and EMT of breast cancer cells by directly targeting S100A2. Oncol Res, 2021, 28(7): 731-744.
21.	Pal M, Bhattacharya S, Kalyan G, et al. Cadherin profiling for therapeutic interventions in epithelial mesenchymal transition (EMT) and tumorigenesis. Exp Cell Res, 2018, 368(2): 137-146.
22.	Li Y, Lv Z, Zhang S, et al. Genetic fate mapping of transient cell fate reveals N-cadherin activity and function in tumor metastasis. Dev Cell, 2020, 54(5): 593-607.e5.
23.	Yang B, Feng X, Liu H, et al. High-metastatic cancer cells derived exosomal miR92a-3p promotes epithelial-mesenchymal transition and metastasis of low-metastatic cancer cells by regulating PTEN/Akt pathway in hepatocellular carcinoma. Oncogene, 2020, 39(42): 6529-6543.
24.	Lu C, Shan Z, Hong J, et al. MicroRNA-92a promotes epithelial-mesenchymal transition through activation of PTEN/PI3K/AKT signaling pathway in non-small cell lung cancer metastasis. Int J Oncol, 2017, 51(1): 235-244.
25.	Liu PJ, Ye YX, Wang YX, et al. MiRNA-92a promotes cell proliferation and invasion through binding to KLF4 in glioma. Eur Rev Med Pharmacol Sci, 2019, 23(15): 6612-6620.

1. Ni D, Teng J, Cheng Y, et al. MicroRNA-92a promotes non-small cell lung cancer cell growth by targeting tumor suppressor gene FBXW7. Mol Med Rep, 2020, 22(4): 2817-2825.
2. Mao QQ, Chen JJ, Xu WJ, et al. miR-92a-3p promotes the proliferation and invasion of gastric cancer cells by targeting KLF2. J Biol Regul Homeost Agents, 2020, 34(4): 1333-1341.
3. Li X, Guo S, Min L, et al. miR-92a-3p promotes the proliferation, migration and invasion of esophageal squamous cell cancer by regulating PTEN. Int J Mol Med, 2019, 44(3): 973-981.
4. Chen L, Shi J, Wu Y, et al. CircRNA CDR1as promotes hepatoblastoma proliferation and stemness by acting as a miR-7-5p sponge to upregulate KLF4 expression. Aging (Albany NY), 2020, 12(19): 19233-19253.
5. Huang Z, Yan Y, Tang P, et al. TEAD4 as a prognostic marker promotes cell migration and invasion of urinary bladder cancer via EMT. Onco Targets Ther, 2021, 14: 937-949.
6. 席剑铭, 张能, 李晓光, 等. 过表达KLF4通过Wnt/β-catenin信号途径调控膀胱癌细胞上皮间质转化及迁移. 中国肿瘤生物治疗杂志, 2019, 26(8): 862-867.
7. Stickeler E, Aktas B, Behrens A, et al. Update breast cancer 2021 part 1—Prevention and early stages. Geburtshilfe Frauenheilkd, 2021, 81(5): 526-538.
8. Plum PS, Warnecke-Eberz U, Drebber U, et al. Upregulation of miR-17-92 cluster is associated with progression and lymph node metastasis in oesophageal adenocarcinoma. Sci Rep, 2019, 9(1): 12113. doi: 10.1038/s41598-019-48624-0.
9. Sand M, Hessam S, Amur S, et al. Expression of oncogenic miR-17-92 and tumor suppressive miR-143-145 clusters in basal cell carcinoma and cutaneous squamous cell carcinoma. J Dermatol Sci, 2017, 86(2): 142-148.
10. Li Y, Lauriola M, Kim D, et al. Adenomatous polyposis coli (APC) regulates miR17-92 cluster through β-catenin pathway in colorectal cancer. Oncogene, 2016, 35(35): 4558-4568.
11. Yang C, Jia X, Zhou J, et al. The miR-17-92 gene cluster is a blood-based marker for cancer detection in non-small-cell lung cancer. Am J Med Sci, 2020, 360(3): 248-260.
12. Lu X, Lu J, Wang S, et al. Circulating serum exosomal miR-92a-3p as a novel biomarker for early diagnosis of gastric cancer. Future Oncol, 2021, 17(8): 907-919.
13. Peng Q, Shen Y, Lin K, et al. Identification of microRNA-92a and the related combination biomarkers as promising substrates in predicting risk, recurrence and poor survival of colorectal cancer. J Cancer, 2019, 10(14): 3154-3171.
14. Yu H, Song H, Liu L, et al. MiR-92a modulates proliferation, apoptosis, migration, and invasion of osteosarcoma cell lines by targeting Dickkopf-related protein 3. Biosci Rep, 2019, 39(4): BSR20190410. doi: 10.1042/BSR20190410.
15. Huang JH, Zhou QH, Chen CC, et al. MicroRNA miR-92a-3p regulates breast cancer cell proliferation and metastasis via regulating B-cell translocation gene 2 (BTG2). Bioengineered, 2021, 12(1): 2033-2044.
16. Wu H, Li S. Long non-coding RNA MT1JP exerts anti-cancer effects in breast cancer cells by regulating miR-92-3p. Gen Physiol Biophys, 2020, 39(1): 59-67.
17. Liu Z, Wu X, Tian Y, et al. Pylori infection induces CXCL8 expression and promotes gastric cancer progress through downregulating KLF4. Mol Carcinog, 2021, 60(8): 524-537.
18. Cannizzaro E, Bannister AJ, Han N, et al. DDX3X RNA helicase affects breast cancer cell cycle progression by regulating expression of KLF4. FEBS Lett, 2018, 592(13): 2308-2322.
19. Zhou H, Liu Y, Zhu R, et al. FBXO32 suppresses breast cancer tumorigenesis through targeting KLF4 to proteasomal degradation. Oncogene, 2017, 36(23): 3312-3321.
20. Wang H, Hu X, Yang F, et al. miR-325-3p promotes the proliferation, invasion, and EMT of breast cancer cells by directly targeting S100A2. Oncol Res, 2021, 28(7): 731-744.
21. Pal M, Bhattacharya S, Kalyan G, et al. Cadherin profiling for therapeutic interventions in epithelial mesenchymal transition (EMT) and tumorigenesis. Exp Cell Res, 2018, 368(2): 137-146.
22. Li Y, Lv Z, Zhang S, et al. Genetic fate mapping of transient cell fate reveals N-cadherin activity and function in tumor metastasis. Dev Cell, 2020, 54(5): 593-607.e5.
23. Yang B, Feng X, Liu H, et al. High-metastatic cancer cells derived exosomal miR92a-3p promotes epithelial-mesenchymal transition and metastasis of low-metastatic cancer cells by regulating PTEN/Akt pathway in hepatocellular carcinoma. Oncogene, 2020, 39(42): 6529-6543.
24. Lu C, Shan Z, Hong J, et al. MicroRNA-92a promotes epithelial-mesenchymal transition through activation of PTEN/PI3K/AKT signaling pathway in non-small cell lung cancer metastasis. Int J Oncol, 2017, 51(1): 235-244.
25. Liu PJ, Ye YX, Wang YX, et al. MiRNA-92a promotes cell proliferation and invasion through binding to KLF4 in glioma. Eur Rev Med Pharmacol Sci, 2019, 23(15): 6612-6620.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The expression of miR-92a in breast cancer tissues and its effect on the migration and invasion behavior of breast cancer cells by targeting regulation of KLF4

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