Ali Imran Alwani

Introduction: Ovarian cancer is a leading cause of death caused by cancer in females^1,2,3, and the stage of the disease determines the prognosis, with a 5-year survival rate for Stage IV cancer being around 20%⁴. As a result, there is a need for biomarkers that would be able to detect ovarian cancer early^1,3. Various long non-coding RNAs (lncRNAs) such as MALAT-1 (Metastasis Associated Lung Adenocarcinoma Transcript 1), which are non-protein-coding RNA molecules that regulate gene transcription, are upregulated in ovarian cancer; however, their mechanisms in modulating disease progression are not completely understood^2,5. Understanding these mechanisms could make lncRNAs valuable therapeutic targets and biomarkers¹. Methods: Reverse transcriptase quantitative PCR (RT-qPCR) was used to determine the expression of MALAT-1 in cell cultures from patients with ovarian cancer⁶. A MALAT-1 knockdown was generated using a siRNA (Small interfering RNA) against MALAT-1 (siMALAT-1)^6,7. A Wound Scratch Assay, the Annexin Apoptosis Detection kit, and propidium iodide were used to determine the rates of cell migration capability, apoptosis, and cell cycle arrest, respectively^6,7. Western Blot analysis was used to determine the expression of phosphatidylinositol-3-kinases (PI3K), Protein Kinase B (Akt), and Matrix Metalloproteases 2 and 9 (MMP2 and MMP9) using antibodies against these proteins⁸. A LASSO (least absolute shrinkage and selection operator) penalized regression test was used to characterize a six-lncRNA signature, including MALAT-1, which divided 311 patients into “high risk” and “low risk” groups based on the predicted recurrence risk⁹. Results: From RT-qPCR, it was determined that MALAT-1 is over-expressed in ovarian cancer cells by more than four-fold (p = 0.001)⁶. From the siMALAT-1 knockdown assays, it was found that the MALAT-1 knockdown is associated with two times decreased cell migration capability, ten-fold increase in apoptosis, and increased G1 cell cycle arrest (p < 0.05)^6,7. From the Western Blot analysis, it was found that the MALAT-1 knockdown is associated with a greater than two-fold decreased expression of PI3K, Akt, and MMP2 and MMP9 (p < 0.05)⁸. The six-lncRNA signature test showed that the “low-risk” patient group had a significantly increased number of disease free days, around 200 days, before recurrence compared to the “high-risk” group (p < 0.0001)⁹. Conclusion: Various lncRNAs such as MALAT-1 are upregulated in ovarian cancer and are involved in promoting tumor proliferation^6,7,8. These lncRNAs could act as potential therapeutic targets and biomarkers that could detect high-risk patients early based on genetic analysis, which could significantly improve prognoses in patients with ovarian cancer^1,9.

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6. Wu L, Wang X, Guo Y. Long non-coding RNA MALAT1 is upregulated and involved in cell proliferation, migration and apoptosis in ovarian cancer. Experimental and Therapeutic Medicine. 2017;13(6):3055-3060.
7. Zhou Y, Xu X, Lv H, et al. The Long Noncoding RNA MALAT-1 Is Highly Expressed in Ovarian Cancer and Induces Cell Growth and Migration. PLoS ONE. 2016;11(5):e0155250.
8. Jin Y, Feng SJ, Qiu S, Shao N, Zheng JH. LncRNA MALAT1 promotes proliferation and metastasis in epithelial ovarian cancer via the PI3K-AKT pathway. European Review for Medical and Pharmacological Sciences. 2017;21(14):3176-3184.
9. Yang K, Hou Y, Li A, et al. Identification of a six-lncRNA signature associated with recurrence of ovarian cancer. Scientific Reports. 2017;7(1):752.