MicroRNA-143 overexpression enhances the chemosensitivity of A172 glioblastoma cells to carmustine.

As an aggressive malignancy, glioblastoma multiforme (GBM) is the most common type of brain tumor. The existing treatments have shown limited achievement in increasing the overall survival of patients. Therefore, identifying the key molecules involved in GBM will provide new potential therapeutic targets. Carmustine is an alkylating agent used as a supplementary therapeutic option for GBM. However, the extensive use of carmustine has been limited by uncertainty about its efficacy. MicroRNAs (miRNAs) are essential in post-transcriptional gene regulation. Many aberrantly expressed miRNAs have been detected in various types of human cancer, including GBM. In this study, we evaluated the potential therapeutic effect of miR-143 in combination with carmustine on GBM cells. A172 cells were transfected with miR-143 mimics and then treated with carmustine. To assess the cell viability, apoptosis induction, and cell cycle progression, the MTT assay, Annexin V/PI apoptosis assay, and flow cytometry were used, respectively. Furthermore, qRT-PCR assay was applied to evaluate the expression level of genes related to apoptosis. The obtained results evidenced that miR-143 transfection could promote the sensitivity of A172 cells to carmustine and enhance carmustine-induced apoptosis via modulating the expression levels of Caspase-3, Caspase-9, Bax, and Bcl-2. Also, our results revealed that combination therapy could effectively diminish cell cycle progression in A172 cells. In conclusion, these results confirmed that miR-143 could enhance carmustine-mediated suppression of cell proliferation and improve the chemosensitivity of A172 cells to this chemotherapeutic agent. Therefore, miR-143 combination therapy may be a promising GBM treatment approach.

The Simultaneous Effects of miR-145-5p and hsa-let-7a-3p on Colorectal Tumorigenesis: In Vitro Evidence.

Purpose: MicroRNAs (miRNAs) are a group of small regulatory non-coding RNAs, which are dysregulated through tumor progression. let-7 and MIR-145 are both tumor suppressor microRNAs that are downregulated in a wide array of cancers including colorectal cancer (CRC). Methods: This study was aimed to investigate the effect of simultaneous replacement of these two tumor suppressor miRNAs on proliferation, apoptosis, and migration of CRC cells. HCT-116 with lower expression levels of hsa-let-7a-3p and MIR-145-5p was selected for functional investigations. The cells were cultured and transfected with hsa-let-7a and MIR-145, separately and in combination. Cell viability and apoptosis rates were assessed by MTT assay and flow cytometry, respectively. Cell cycle status was further evaluated using flow cytometry and qRT-PCR was employed to evaluate gene expression. Results: The obtained results showed that exogenous overexpression of MIR-145 and hsa-let-7a in HCT-116 cells could cooperatively decrease CRC cell proliferation and induce sub-G1 cell cycle arrest. Moreover, hsa-let-7a and MIR-145 co-transfection significantly increased apoptosis induction compared to separate transfected cells and control through modulating the expression levels of apoptosis-related genes including Bax, Bcl-2, P53, Caspase-3, Caspase-8, and Caspase-9. Furthermore, qRT-PCR results illustrated that hsa-let-7a and MIR-145 combination more effectively downregulated MMP-9 and MMP-2 expression, as the important modulators of metastasis, compared to the controls. Conclusion: Taken together, considering that exogenous overexpression of MIR-145 and hsa-let-7a showed cooperative anti-cancer effects on CRC cells, their combination may be considered as a novel therapeutic strategy for the treatment of CRC.

The function of miR-145 in colorectal cancer progression; an updated review on related signaling pathways.

MicroRNAs (miRNA) are a broad class of small, highly conserved non-coding RNAs that largely influence gene expression after transcription through binding to various target mRNAs. miRNAs are frequently dysregulated in a wide array of human cancers, possessing great value as diagnostic and therapeutic targets. miR-145, as promising tumor suppressor miRNA, also exhibits deregulated expression levels in human malignancies and participates in various processes, including cell proliferation, apoptosis, migration and differentiation. In particular, miR-145 has been shown to be downregulated in colorectal cancer (CRC), which in turn leads to cell growth, invasion, metastasis and drug resistance. Furthermore, miR-145 is involved in the regulation of multiple tumor specific signaling pathways, such as KRAS and P53 signaling by targeting various genes through colorectal tumorigenesis. Therefore, considering its diagnostic and therapeutic potential, it was aimed to present the recent finding focusing on miR-145 functions to better understand its involvement in CRC incidence and progression through interplay with various signaling pathways. This study is based on articles indexed in PubMed and Google scholar until 2021.

MicroRNA-143 Sensitizes Cervical Cancer Cells to Cisplatin: a Promising Anticancer Combination Therapy.

Cisplatin-based chemotherapy is commonly used for cervical cancer treatment. However, the development of chemoresistance is considered the main obstacle to the effectiveness of this therapeutic agent. MicroRNAs are illustrated to play a major role in the regulation of cancer cell chemosensitivity. Therefore, this study was aimed to investigate the potential therapeutic role of miRNA-143 in combination with cisplatin on cervical cancer cells. Then, CaSki cell line with low expression levels of miRNA-143 was selected for functional experiments. The cells were treated with miRNA-143 and cisplatin individually or in combination. The cell viability and apoptosis induction were evaluated by MTT, Annexin V-FITC/PI, and DAPI staining tests. Cell migration was further evaluated by wound healing assay. The effect of miRNA-143 and cisplatin combination on gene expression was quantified by real-time PCR. Furthermore, the combination therapy effect on cell cycle progression and autophagy induction was also evaluated by flow cytometry. Our results showed that miRNA-143 overexpression could increase cisplatin-induced apoptosis and increase the sensitivity of CaSki cells to low doses of this chemotherapeutic agent via modulating the expression of apoptosis-related genes including Bcl-2, Bax, and caspase-9. Besides, miRNA-143 and cisplatin were demonstrated to cooperatively increase the cell cycle arrest at the sub-G1 and G2-M phases, induce autophagy activation, and via downregulation of vimentin inhibit CaSki cell migration. Moreover, c-Myc as an important regulator of cell growth was downregulated in treatment groups compared to the control. In conclusion, regarding that miRNA-143 could sensitize cervical cancer cells to cisplatin, it may be considered a promising therapeutic strategy for the treatment of this malignancy.