# Feedback Modulation between Human IN080 Chromatin Remodeling Complex and miR-372 in HCT116 Cells
Accordingly, several primarily diagnosed cancer types have been reported to express miR-371-373 abnormally. It is important to note that miR-371-373 expression levels differ depending on the kind of cancer. For example, the expression of miR-372-373 is found to be significantly reduced in non-small cell lung cancer [11], pancreatic cancer [16], prostate cancer [17], cervical cancer tissues [18], endometrial cancer [19], and ovarian carcinoma [20] as compared to normal tissues. On the other hand, miR-372 was found overexpressed in several tumor tissues compared to normal tissues, including esophageal squamous cell carcinoma [13], lung squamous cell carcinoma [21], oral squamous cell carcinoma [22], hepatocellular carcinoma [23], and glioma [24]. It is worth noting that several studies have reported contradictory results for miR-372 expression in breast cancer tissues and CRC: reduced miR-372 expression in 20 and 45 primary breast cancer and CRC tissues compared to paired normal tissues was reported [25; 26], respectively, whereas increased miR-372 expression in the same type of cancer tissues was also reported [27; 28], highlighting the complexity of the molecular mechanism of miRNAs in tumorigenesis. In a word, the expression of miRNAs and the genes they regulate are strongly linked to cancer. Growing evidence shows that miR-372 regulates many important biological processes in cells, such as cell proliferation, apoptosis, migration, and invasion, in many human cancers [29]. MiR-372 may operate as tumor suppressors by inhibiting oncogene expression or as oncogenic miRNAs by repressing the expression of tumor suppressor genes. For example, miR-372 promotes the proliferation of CRC, breast cancer, and gastric cancer cells by binding to target sites in the 3\({}^{\prime}\)-UTR of large tumor suppressor homolog 2 (_LATS2_) [30]. In addition, miR-372 plays an oncogenic function by down-regulating fibroblast growth factor 9 (_FGF9_) and _p62_, respectively, in both lung squamous and head and neck squamous cell carcinoma [21; 31]. On the contrary, miR-372 functions as a tumor suppressor by targeting and binding to complementary sequences in the 3\({}^{\prime}\)-UTRs of genes, such as FXYD domain containing ion transport regulator 6 (_FXYD6_), inhibiting growth and metastasis in different cancer cells, including osteosarcoma, renal cell carcinoma, prostate cancer, hepatocellular carcinoma, breast cancer, and cervical cancer cells [32]. However, there are few reports on the relationship between miR-372 expression or its function and epigenetic regulation. The human INO80 chromatin remodeling complex composed of 15 subunits catalyzes ATP-dependent sliding of nucleosomes along DNA. Its eight core subunits (Arp5, Arp8, TIP49a/b, Ies2, Ies6, Arp4, and YY1) are highly evolutionarily conserved from _yeast_ to humans and form an enzymatic core, including HSA (helicase-SANT-associated domain) and SNF2 (SWI/SNF catalytic subunit 2) module [33; 34]. Therefore, dysfunction of any of the catalytic subunits of INO80 or the enzyme core may affect the biological function of the entire complex of INO80 [35; 36]. Based on gene expression profiles from the knockdown of _INO80-_, _Arp8-_, _Arp5-_, _Ies6-_, and _Ies2_ in HeLa cells, we found that hundreds of genes were co-regulated by silencing the SNF2 (Arp5, Ies6, and Ies2) and HSA (Arp8) modules. Among the gene expression profiles, upregulation of miR372 was found in INO80 complex key subunits knockdown gene profiles. In line with this, two YY1-binding sites were identified upstream of the miR-372 transcription start site, and upregulation of miR-372 was found in siYY1 treated MCF-7 breast cancer cells (YY1 is known to be one of the key subunits of the INO80 complex) [37]. Therefore, we speculate a tight relationship between the INO80 complex and miR-372.