Background and Aim: miR-29b2 and miR-29c play a suppressive role in breast cancer progression. Mir29b2chg/C1orf132 is the host gene for generating both microRNAs. However, there existed longer transcripts of the gene, with unknown function. Methods: Here, we have employed bioinformatics and experimental approaches to decipher expression of two different C1orf132 transcripts in different types of breast cancer cell lines and tissues. Results: Our data demonstrated a significant downregulation of C1orf132 in triple-negative type of breast cancer. We also find out that a mouse homolog of C1orf132 is located at a similar genomic location as its human counterpart, between CD46 and CD34 genes. Conclusion: The latter finding suggests new potential functions for the lncRNA, other than being a simple miR-29 host gene. We predicted a putative promoter for the longer transcripts of C1orf132. The functionality of the distal promoter confirmed by transfecting MCF7 cells with a C1orf132 promoter-GFP construct. Knocking-down the promoter by means of the Crispr/Cas9 approach revealed no alteration in the expression level of neighboring genes, CD46 and CD34. However, the expression level of miR-29c was reduced by half, suggesting an enhancer effect of the distal promoter on miR-29cf generation. Furthermore, the promoter knock-down revealed a G2/M cell cycle arrest and an elevation of migration ability in Mcf12a edited cells. Moreover, the expression of cell mobility genes e.g. CDH2, FGF2, FGFR1 and the stem cell and EMT -associated transcription factor ZEB1 was significantly overexpressed in edited cells. Altogether, we are reporting here the existence of an additional/distal promoter with an enhancer effect on miR-29 generation and an inhibitory effect on cell proliferation and cell migration.

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