MiR-96-5p Facilitates Lung Adenocarcinoma Cell Phenotypes by Inhibiting FHL1

Overview

Journal Comput Math Methods Med

Publisher Hindawi

Specialty Medical Informatics

Date 2022 Aug 26

PMID 36017148

Authors

Feng Zhou

Chaojie Qian

Tingting Chen

Xiaoliang Zang

Affiliations

Soon will be listed here.

Abstract

Objective: FHL1 is understood as a tumor repressor gene in various cancers and a possible target for cancer treatment. We investigated the influences of FHL1 on cell functions as well as its molecular mechanisms in lung adenocarcinoma (LUAD) cells.

Methods: The miRNA-mRNA modulatory axis was predicted by bioinformatics. The expression levels of FHL1 mRNA and protein in LUAD cells were, respectively, analyzed by qRT-PCR and western blot. Dual luciferase analysis was introduced to verify the interaction between miR-96-5p and FHL1. CCK-8, cell colony formation, and Transwell assays were utilized to analyze proliferation, colony formation, migration, and invasion of A549 cells.

Results: Expression of FHL1 mRNA and protein in LUAD tissue and cells was downregulated, which was linked with poor prognoses of patients. In addition, FHL1 overexpression could hamper colony formation, proliferation, invasion, and migration of LUAD cells. In addition, dual-luciferase analysis verified miR-96-5p as an upstream regulator of FHL1. Overexpression of miR-96-5p suppressed FHL1 expression in LUAD cells and promoted proliferation, invasion, and migration of LUAD cells, while overexpression of FHL1 could simultaneously restore the above-mentioned promoting effect.

Conclusion: MiR-96-5p fostered cell malignant behaviors by targeting FHL1. This research uncovered the regulatory mechanism of FHL1 in LUAD and offered optional therapeutic targets for LUAD patients.

Citing Articles

Role of four and a half LIM domain protein 1 in tumors (Review).

Tao Y, Wu Y, Shen R, He S, Miao X Oncol Lett. 2024; 29(1):37.

PMID: 39512507 PMC: 11542161. DOI: 10.3892/ol.2024.14783.

MicroRNA‑mediated regulation in lung adenocarcinoma: Signaling pathways and potential therapeutic implications (Review).

Liu J, Zhang F, Wang J, Wang Y Oncol Rep. 2023; 50(6).

PMID: 37859595 PMC: 10603552. DOI: 10.3892/or.2023.8648.

A potential tumor marker: Chaperonin containing TCP‑1 controls the development of malignant tumors (Review).

Zheng L, Chen X, Zhang L, Qin N, An J, Zhu J Int J Oncol. 2023; 63(3).

PMID: 37539774 PMC: 10552740. DOI: 10.3892/ijo.2023.5554.

References

Wang J, Huang F, Huang J, Kong J, Liu S, Jin J . Epigenetic analysis of FHL1 tumor suppressor gene in human liver cancer. Oncol Lett. 2017; 14(5):6109-6116. PMC: 5661399. DOI: 10.3892/ol.2017.6950. View

Ding L, Niu C, Zheng Y, Xiong Z, Liu Y, Lin J . FHL1 interacts with oestrogen receptors and regulates breast cancer cell growth. J Cell Mol Med. 2009; 15(1):72-85. PMC: 3822495. DOI: 10.1111/j.1582-4934.2009.00938.x. View

Greenawalt E, Edmonds M, Jain N, Adams C, Mitra R, Eischen C . Targeting of SGK1 by miR-576-3p Inhibits Lung Adenocarcinoma Migration and Invasion. Mol Cancer Res. 2018; 17(1):289-298. PMC: 6318035. DOI: 10.1158/1541-7786.MCR-18-0364. View

Pereira C, de Carvalho A, Silva F, Melendez M, Lessa R, Andrade V . In vitro and in silico validation of CA3 and FHL1 downregulation in oral cancer. BMC Cancer. 2018; 18(1):193. PMC: 5816396. DOI: 10.1186/s12885-018-4077-3. View

Zhao M, Xin X, Zhang J, Dai W, Lv T, Song Y . LncRNA GMDS-AS1 inhibits lung adenocarcinoma development by regulating miR-96-5p/CYLD signaling. Cancer Med. 2019; 9(3):1196-1208. PMC: 6997056. DOI: 10.1002/cam4.2776. View

Fei L, Huang W, Wang Y, Lei L, Li Z, Zheng Y . PRDM16 functions as a suppressor of lung adenocarcinoma metastasis. J Exp Clin Cancer Res. 2019; 38(1):35. PMC: 6347838. DOI: 10.1186/s13046-019-1042-1. View

Iwai N, Yasui K, Tomie A, Gen Y, Terasaki K, Kitaichi T . Oncogenic miR-96-5p inhibits apoptosis by targeting the caspase-9 gene in hepatocellular carcinoma. Int J Oncol. 2018; 53(1):237-245. DOI: 10.3892/ijo.2018.4369. View

Wang Z, Zhang J, Yang B, Li R, Jin L, Wang Z . Long Intergenic Noncoding RNA 00261 Acts as a Tumor Suppressor in Non-Small Cell Lung Cancer via Regulating miR-105/FHL1 Axis. J Cancer. 2019; 10(25):6414-6421. PMC: 6856729. DOI: 10.7150/jca.32251. View

Fan Z, Xu X, Zhang X, Wang T, Han B, Liang Y . [FHL1 knockdown mediated by lentiviral shRNA promotes the growth of HeLa and HepG2 cells]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2015; 31(7):879-83. View

10.

Wang J, Zou K, Feng X, Chen M, Li C, Tang R . Downregulation of NMI promotes tumor growth and predicts poor prognosis in human lung adenocarcinomas. Mol Cancer. 2017; 16(1):158. PMC: 5639741. DOI: 10.1186/s12943-017-0705-9. View

11.

Feng Y, Liu C, Xue Y, Chen Y, Wang Y, Wu X . MicroRNA-147b promotes lung adenocarcinoma cell aggressiveness through negatively regulating microfibril-associated glycoprotein 4 (MFAP4) and affects prognosis of lung adenocarcinoma patients. Gene. 2019; 730:144316. DOI: 10.1016/j.gene.2019.144316. View

12.

Zhao L, Yu Z, Zhao B . Mechanism of VIPR1 gene regulating human lung adenocarcinoma H1299 cells. Med Oncol. 2019; 36(11):91. DOI: 10.1007/s12032-019-1312-y. View

13.

Zhou H, Wu C, Bi E . MiR-96-5p inhibition induces cell apoptosis in gastric adenocarcinoma. World J Gastroenterol. 2019; 25(47):6823-6834. PMC: 6931005. DOI: 10.3748/wjg.v25.i47.6823. View

14.

Wang Y, Chen T, Huang H, Jiang Y, Yang L, Lin Z . miR-363-3p inhibits tumor growth by targeting PCNA in lung adenocarcinoma. Oncotarget. 2017; 8(12):20133-20144. PMC: 5386750. DOI: 10.18632/oncotarget.15448. View

15.

Li S, Hu Y, Zhao J, Zang J, Fei Z, Han H . Downregulation of FHL1 protein in glioma inhibits tumor growth through PI3K/AKT signaling. Oncol Lett. 2020; 19(6):3781-3788. PMC: 7202308. DOI: 10.3892/ol.2020.11476. View

16.

Ren W, Lian P, Cheng L, Du P, Guan X, Wang H . FHL1 inhibits the growth of tongue squamous cell carcinoma cells via G1/S cell cycle arrest. Mol Med Rep. 2015; 12(3):3958-3964. DOI: 10.3892/mmr.2015.3844. View

17.

Liu Z, Wu Z, Li W, Wang L, Wan J, Zhong Y . MiR-96-5p promotes the proliferation, invasion and metastasis of papillary thyroid carcinoma through down-regulating CCDC67. Eur Rev Med Pharmacol Sci. 2019; 23(8):3421-3430. DOI: 10.26355/eurrev_201904_17706. View

18.

Cao W, Liu J, Xia R, Lin L, Wang X, Xiao M . X-linked FHL1 as a novel therapeutic target for head and neck squamous cell carcinoma. Oncotarget. 2016; 7(12):14537-50. PMC: 4924734. DOI: 10.18632/oncotarget.7478. View

19.

Han S, Cui C, He H, Shen X, Chen Y, Wang Y . FHL1 regulates myoblast differentiation and autophagy through its interaction with LC3. J Cell Physiol. 2019; 235(5):4667-4678. DOI: 10.1002/jcp.29345. View

20.

Xie S, Liu G, Huang J, Hu H, Jiang W . miR-210 promotes lung adenocarcinoma proliferation, migration, and invasion by targeting lysyl oxidase-like 4. J Cell Physiol. 2019; 234(8):14050-14057. DOI: 10.1002/jcp.28093. View