Long Non-coding RNA OSTM1-AS1 Promotes Renal Cell Carcinoma Progression by Sponging MiR-491-5p and Upregulating MMP-9

Overview

Journal Sci Rep

Specialty Science

Date 2025 Jan 2

PMID 39747324

Authors

Jun-Feng Chen

Sha-Zhou Ye

Ke-Jie Wang

Xiang-Yu Meng

Bin-Bin Yang

Ke Rong Wu

Qi Ma

Affiliations

Soon will be listed here.

Abstract

Long noncoding RNAs (lncRNAs) have been recognized as essential regulators in various human malignancies. Hundreds of lncRNAs were known to be abnormally expressed in renal cell carcinoma (RCC) through a lncRNA expression microarray, among which lncRNA OSTM1 antisense RNA 1(OSTM1-AS1) was revealed as one of the most abundant lncRNAs. However, the function of OSTM1-AS1 in RCC remains unknown. Here, we examined OSTM1-AS1 functional roles and mechanism in RCC development. OSTM1-AS1 expression was significantly highly expressed among RCC tissue specimens and cell lines. Functionally, OSTM1-AS1 knockdown significantly suppressed cell proliferation, migration along with metastasis of RCC cells. Mechanistically, miR-491-5p was targeted via OSTM1-AS1, and down-regulation of miR-491-5p reversed OSTM1-AS1 knockdown impact on RCC migration and invasion. MMP-9 was targeted via miR-491-5p, and MMP-9 overexpression reversed miR-491-5p or OSTM1-AS1 knockdown impact on cell migration and invasion. MMP-9 abundance was decreased by OSTM1-AS1 silence, that was reduced by miR-491-5p deficiency. Importantly, our investigation revealed that OSTM1-AS1 has the ability to interact with miR-491-5p, thereby increasing the MMP-9 expression. The in vivo trial demonstrated that OSTM1-AS1 suppression resulted in tumor growth inhibition among nude mice. In summary, our findings indicate, for the first time, at least to the best of our knowledge, that OSTM1-AS1 serves as an oncogene among RCC by promoting proliferation, invasion, and metastasis through its targeting of the miR-491-5p/MMP9 axis. Therefore, this axis could represent a promising alternative therapeutic target for RCC treatment.

References

Yu Z, Tang H, Chen S, Xie Y, Shi L, Xia S . Exosomal LOC85009 inhibits docetaxel resistance in lung adenocarcinoma through regulating ATG5-induced autophagy. Drug Resist Updat. 2023; 67:100915. DOI: 10.1016/j.drup.2022.100915. View

Gonzalez-Avila G, Sommer B, Mendoza-Posada D, Ramos C, Garcia-Hernandez A, Falfan-Valencia R . Corrigendum to "Matrix metalloproteinases participation in the metastatic process and their diagnostic and therapeutic applications in cancer" [Crit. Rev. Oncol. Hematol. 137, May (2019) 57-83]. Crit Rev Oncol Hematol. 2019; 138:172. DOI: 10.1016/j.critrevonc.2019.04.017. View

Zeng J, Li Y, Wang Y, Xie G, Feng Q, Yang Y . lncRNA 00312 Attenuates Cell Proliferation and Invasion and Promotes Apoptosis in Renal Cell Carcinoma via miR-34a-5p/ASS1 Axis. Oxid Med Cell Longev. 2020; 2020:5737289. PMC: 7140129. DOI: 10.1155/2020/5737289. View

Meng W, Cao X, Sun W, Zheng L, Fan B, Zhou S . A functional polymorphism at the miR‑491‑5p binding site in the 3'‑untranslated region of the MMP‑9 gene increases the risk of developing ventilator‑associated pneumonia. Int J Mol Med. 2021; 48(6). DOI: 10.3892/ijmm.2021.5050. View

Cairns P . Renal cell carcinoma. Cancer Biomark. 2011; 9(1-6):461-73. PMC: 3308682. DOI: 10.3233/CBM-2011-0176. View

Gupta S, Tripathi Y . Potential of long non-coding RNAs in cancer patients: From biomarkers to therapeutic targets. Int J Cancer. 2016; 140(9):1955-1967. DOI: 10.1002/ijc.30546. View

Kallakury B, Karikehalli S, Haholu A, Sheehan C, Azumi N, Ross J . Increased expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinases 1 and 2 correlate with poor prognostic variables in renal cell carcinoma. Clin Cancer Res. 2001; 7(10):3113-9. View

Shi J, Zhang D, Zhong Z, Zhang W . lncRNA ROR promotes the progression of renal cell carcinoma through the miR‑206/VEGF axis. Mol Med Rep. 2019; 20(4):3782-3792. PMC: 6755161. DOI: 10.3892/mmr.2019.10636. View

Su Y, Lu J, Chen X, Liang C, Luo P, Qin C . Long non-coding RNA HOTTIP affects renal cell carcinoma progression by regulating autophagy via the PI3K/Akt/Atg13 signaling pathway. J Cancer Res Clin Oncol. 2018; 145(3):573-588. DOI: 10.1007/s00432-018-2808-0. View

10.

Pan J, Fang S, Tian H, Zhou C, Zhao X, Tian H . lncRNA JPX/miR-33a-5p/Twist1 axis regulates tumorigenesis and metastasis of lung cancer by activating Wnt/β-catenin signaling. Mol Cancer. 2020; 19(1):9. PMC: 6961326. DOI: 10.1186/s12943-020-1133-9. View

11.

Gonzalez-Avila G, Sommer B, Mendoza-Posada D, Ramos C, Garcia-Hernandez A, Falfan-Valencia R . Matrix metalloproteinases participation in the metastatic process and their diagnostic and therapeutic applications in cancer. Crit Rev Oncol Hematol. 2019; 137:57-83. DOI: 10.1016/j.critrevonc.2019.02.010. View

12.

Xue S, Wang S, Li J, Guan H, Jiang S, Guo Y . LncRNA NBAT1 suppresses cell proliferation and migration via miR-346/GSK-3β axis in renal carcinoma. IUBMB Life. 2019; 71(11):1720-1728. DOI: 10.1002/iub.2111. View

13.

Liu F, Zhang H, Xie F, Tao D, Xiao X, Huang C . Hsa_circ_0001361 promotes bladder cancer invasion and metastasis through miR-491-5p/MMP9 axis. Oncogene. 2019; 39(8):1696-1709. DOI: 10.1038/s41388-019-1092-z. View

14.

Wu K, Hu L, Lv X, Chen J, Yan Z, Jiang J . Long non-coding RNA MIR4435-1HG promotes cancer growth in clear cell renal cell carcinoma. Cancer Biomark. 2020; 29(1):39-50. DOI: 10.3233/CBM-201451. View

15.

Yu T, Wang L, Li W, Zuo Q, Li M, Zou Q . Downregulation of miR-491-5p promotes gastric cancer metastasis by regulating SNAIL and FGFR4. Cancer Sci. 2018; 109(5):1393-1403. PMC: 5980274. DOI: 10.1111/cas.13583. View

16.

Mondal S, Adhikari N, Banerjee S, Amin S, Jha T . Matrix metalloproteinase-9 (MMP-9) and its inhibitors in cancer: A minireview. Eur J Med Chem. 2020; 194:112260. DOI: 10.1016/j.ejmech.2020.112260. View

17.

Lin Y, Lee L, Lee W, Chu C, Tan P, Yang Y . Melatonin inhibits MMP-9 transactivation and renal cell carcinoma metastasis by suppressing Akt-MAPKs pathway and NF-κB DNA-binding activity. J Pineal Res. 2016; 60(3):277-90. DOI: 10.1111/jpi.12308. View

18.

Xu Y, Hou R, Lu Q, Zhang Y, Chen L, Zheng Y . MiR-491-5p negatively regulates cell proliferation and motility by targeting PDGFRA in prostate cancer. Am J Cancer Res. 2018; 7(12):2545-2553. PMC: 5752694. View

19.

Veys C, Jammes M, Redini F, Poulain L, Denoyelle C, Legendre F . Tumor Suppressive Role of miR-342-5p and miR-491-5p in Human Osteosarcoma Cells. Pharmaceuticals (Basel). 2022; 15(3). PMC: 8949568. DOI: 10.3390/ph15030362. View

20.

Mercer T, Dinger M, Mattick J . Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009; 10(3):155-9. DOI: 10.1038/nrg2521. View